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German Center for Infection Research
ANNUAL REPORT
2013
1
DZIF at a glance
The German Center for Infection Research (DZIF) coordinates and oversees the strategic
planning of translational infection research within Germany.
Its mission is to translate the results from basic biomedical research into clinical research.
32 DZIF research centres are working concertedly against the global threat presented by
infectious diseases.
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Table of contents
Editorial 3
About DZIF 4
Science – Translation in focus
Emerging Infections 6
Tuberculosis 8
Malaria 10
HIV 12
Hepatitis 14
Gastrointestinal Infections 16
Infections of the immunocompromised Host 18
Healthcare-associated and Antibiotic-resistant bacterial Infections 20
Novel Antiinfectives 22
Research infrastructures
Product Development Unit 24
Clinical Trial Unit 25
African Partner Sites 26
Natural Compound Library 27
Biobanking 28
Bioinformatics 29
DZIF Academy 30
Collaborations in DZIF 31
DZIF Highlights 2013 32
Science and public 34
External collaborations 36
German Health Research Centres 39
Facts and figures
Organisations and bodies 40
Partner sites and member establishments 42
Finance 46
Personnel und awards 48
Publications 50
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Editorial
Yet we may have rested on our laurels for too long and antiinfectives could become victims of their own success. An
increasing number of pathogens are becoming resistant to the available medicines. The loss of control over infectious
diseases is unsettling researchers, clinicians and the entire healthcare system alike.
These and other global challenges relating to infection are at the core of DZIF’s endeavours. In addition to developing
new approaches for the diagnosis and therapy of the most important healthcare-related infectious diseases worldwide,
DZIF is paying special attention to emerging pathogens, nosocomial infections in the immunocompromised host and the
development of novel candidate antimicrobial agents.
Specialised competence centres within DZIF are dedicated to these topics, where clinical infectiologists and basic researchers from different establishments collaborate closely. This networking of universities, university medical centres and
non-university research establishments into competence centres combines expertise, creates synergies and allows rapid
translation into clinical practice.
The results selected for this Annual Report illustrate the paths we have taken, from releasing a new malaria vaccine, to
‘antibiotic stewardship’ for containing bacterial resistance, to our dedication to educating qualified physicians and scientists in infection research. All these activities of the past three years demonstrate the new translational potential of the
institutes cooperating within DZIF.
DZIF e.V. Executive Board
Prof Dr Martin Krönke
Prof Dr Ulrike Protzer
Prof Dr Dirk Heinz
Editorial
In the middle of last century, antibiotics revolutionised medicine and all but eliminated the threat posed by many bacterial
infectious diseases. Improved hygiene and prophylactic vaccines against infections have saved more human lives than all
other medical interventions. Without these accomplishments, today’s advanced and intensive medicine would be inconceivable.
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About DZIF
About DZIF
DZIF: New integrative and
interdisciplinary research approaches
In spite of antibiotics and vaccinations, infections are still
a major threat to human health worldwide. Alongside
chronic and poverty-associated infectious diseases, we
also face newly emerging microbial and viral infections.
Posing another serious threat are the resistances pathogens are developing against the conventional antibiotics
in use. And there is another problem. In industrial countries, especially, advanced medicine is actually clearing
a path for infections in medically immunosuppressed
patients, especially in the fields of transplant medicine
and oncology.
In light of all this, the German Center for Infection
Research (Deutsches Zentrum für Infektionsforschung,
DZIF) is taking an integrative approach. It brings experts
in translational research, epidemiology and clinical practice together to share their insights. Cooperating within
DZIF, with funding from the German Federal Government and Länder, are universities, university medical
centres, Leibnitz and Max Planck Institutes, Helmholtz
Centres and Federal research establishments with strong
profiles in the field of infectious diseases.
Competence centres with international visibility
DZIF’s mission is to coordinate and strategically align
translational infection research in Germany – i.e. research
at the preclinical–clinical interface. DZIF is thereby making a substantial contribution towards the effective and
efficient development of new diagnostic, preventive and
therapeutic methods for treating infectious diseases.
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… DZIF overcomes institutional boundaries
DZIF also serves as a link between basic research and the
biotech and pharmaceutical industry. Good manufacturing
practice (GMP), good laboratory practice (GLP), validated
animal models and professionally-designed clinical trials
are core components of the DZIF concept. The centre
is a common contact for national authorities such as the
Robert Koch, Friedrich Löffler and Paul Ehrlich Institutes,
as well as the Federal Institute for Drugs and Medical
Devices, with which research activities are coordinated or
jointly conducted.
Preclinical and clinical research
DZIF puts German infection research in a position to continue targeted development of fundamental findings in a
preclinical and clinical direction. Advancements in translational research will allow DZIF and other institutions in the
public and private health sectors to develop new diagnostic
methods, anti-infectives and vaccines. The effectiveness
of DZIF’s operations can be seen from the example of
the newly emerged “Middle East respiratory syndrome
coronavirus” (MERS-CoV). DZIF was instrumental in
developing a diagnostic assay and a vaccine for MERSCoV. Representatives from various TTUs are available as
advisors in Saudi Arabia. Together, the DZIF scientists are
helping to curb MERS and other infectious diseases and
provide timely help to patients.
DZIF groups its research activities into nine Thematic Translational Units (TTU) and six interdisciplinary
Translational Infrastructures (TI):
Thematic Translational Units (TTU)
•
•
•
•
•
•
•
•
Emerging Infections
Tuberculosis
Malaria
HIV
Hepatitis
Gastrointestinal Infections
Infections of the immunocompromised Host
Healthcare-associated and Antibiotic-resistant
bacterial Infections
• Novel Antiinfectives
Translational Infrastructures (TI)
•
•
•
•
•
•
Product Development Unit
Clinical Trial Units
African Partner Sites
Natural Compound Library
Biobanking
Bioinformatics
• DZIF Academy
About DZIF
Infections know no national boundaries …
Cross-border collaboration is of pivotal importance at
DZIF. Given that most infections occur worldwide and
the health systems of developing and newly-industrialised
countries are facing major problems, DZIF systematically
involves partners from international organizations and
from countries on the African continent, in particular, in its
work.
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Emerging Infections
Science – Translation in focus
Broad-spectrum war on viruses
Safety clothing is mandatory when handling little-researched pathogens.
Epidemics of new infectious diseases require rapid intervention to prevent them from spreading any further.
In the TTU “Emerging Infections” of DZIF, scientists
from universities, university clinics and the public
health service are collaborating closely to research and
combat such diseases.
In the summer of 2012, a 60-year-old man died in Jeddah, Saudi Arabia, after nearly three weeks of suffering
from lung and kidney failure. It all started with harmless
cold-like symptoms. Found lurking in the patient’s bronchial secretions was the previously unknown Middle East
respiratory syndrome coronavirus (MERS-CoV). By the
end of 2013, 176 people had already fallen ill with MERS.
Researchers at DZIF’s Bonn-Cologne site quickly developed the standard test for high-certainty detection
of MERS in 2012, working from genome sequences.
Then, in 2013, DZIF scientists led by Prof Gerd Sutter of
Ludwig-Maximilians-Universität München started working on developing a vaccine. For this, they used tested,
safe vaccination viruses.
MERS vaccine within reach
They genetically manipulated the viruses to produce the
same envelope protein as MERS-CoV. In infected host
cells, it becomes anchored in the cell membrane and
stimulates MERS-CoV-specific immune responses after
vaccination. The Erasmus Medical Center Rotterdam and
Philipps-Universität Marburg were also involved in the
research work. In mice, the test vaccine based on Modified Vaccinia virus Ankara (MVA) promotes the formation
of antibodies that effectively block cell infection with
MERS-CoV. Now the researchers need a suitable animal
model that mimics the human disease more closely, since
mice do not naturally fall ill from MERS. “Development of
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New mosquitoes and parasites in Germany
In a large-scale monitoring programme led by Prof Egbert
Tannich und Dr Jonas Schmidt-Chanasit, scientists at the
Bernhard Nocht Institute for Tropical Medicine in Hamburg recorded the populations of mosquitoes in Germany
and the pathogens they carry. With the support of various cooperation partners, a total of 130,000 mosquitoes
were studied in 2013. The researchers discovered that
the Asian tiger mosquito (Aedes albopictus) is regularly
carried from southern Europe into southern Germany
with road traffic. This mosquito can carry tropical viral
diseases such as dengue and chikungunya fever. In Brandenburg and Saxony-Anhalt, the researchers detected
larvae of the canine skin worm Dirofilaria repens in three
mosquito species. This parasite occurs in dogs, the weasel
family and foxes in southern and eastern Europe, Africa
and Asia. Infected mosquitoes can also infect humans.
“A locally acquired Dirofilaria infection was recorded for
the first time recently in a patient from Saxony-Anhalt.
Exactly how at-risk of contraction people are in Germany
will have to be investigated in further epidemiological
studies,” Tannich reports.
Other research focuses of the TTU are the immunological and epidemiological characteristics of emerging
infectious diseases and their clinical treatment. Rapid and
reliable methods for detecting new pathogens must be
developed and guidelines established on how to proceed
with infected patients. The TTU also intends to develop new broad-spectrum antiviral medicines and active
agents against diseases such as dengue fever and West
Nile fever.
Coordinator: Prof Dr Stephan Becker, Marburg
• New viral diseases are emerging continually and in
most cases unexpectedly. One current example is
the Middle East respiratory syndrome coronavirus
(MERS-CoV).
• They require rapid intervention to prevent them from
spreading.
• Pathogens and new mosquito species are introduced
into Europe by travel and freight transport.
• Mosquitos are transmitting exotic diseases more
frequently throughout Europe. These include dengue,
West Nile and chikungunya fever and Malaria tertiana.
Science – Translation in focus
an approved vaccine against MERS-CoV will likely take
several more years, since it has to go through several
clinical trial phases before approval,” Sutter explains.
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Tuberculosis
Science – Translation in focus
Resistant pathogens in the spotlight
A tuberculosis patient is in good hands at the Medical Clinic Borstel.
German tuberculosis researchers are among the best in
the world. To ensure their results are applied more rapidly for the benefit of patients, the TTU “Tuberculosis”
of DZIF was created. Results from basic research flow
directly into the prevention, diagnosis and therapy of
tuberculosis. The TTU includes DZIF Munich, Tübingen,
Hannover-Braunschweig and Hamburg-Lübeck-Borstel.
The researchers are concentrating above all on combatting multidrug-resistant and extensively drug-resistant
pathogens of M/XDR tuberculosis, which are resistant
to conventional antibiotics. Important aims are effective protection against M/XDR tuberculosis and better
treatment for patients.
Treatment of M/XDR tuberculosis has so far been of limited success. The drugs used are expensive and often have
severe side-effects. While the World Health Organization
recommends combination therapy over 20 months for
all patients, many patients stop their therapy before the
end of the full term. As a consequence, the disease breaks
out anew. How long treatment has to continue in each
case is unpredictable and can vary substantially between
individuals. As part of the TTU‘s work, scientists at the
Research Center Borstel are looking for ways to adapt
the treatment optimally to each patient and reduce the
stress of side-effects. To this end, they are identifying
biomarkers that reveal how the body responds to the therapy. Alongside immunological parameters, chemists are
studying lipids as a novel biomarker in patient samples. To
verify their suitability, the researchers have recruited a
cohort of M/XDR tuberculosis patients throughout all of
Germany, whose progress on therapy will be monitored
and analysed.
Basic research and clinical practice closely linked
At the medical clinic of the Research Center Borstel, an
area has been set aside for the inpatient and outpatient
care of tuberculosis patients. The results from basic
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• Tuberculosis is caused by bacteria of the Mycobacterium tuberculosis complex.
• Worldwide around 8 million new cases are recorded
each year, with 1.4 million fatalities. Trend: gradually
declining.
• The increase of multidrug-resistant strains that are
especially difficult to treat is a major problem. Trend:
dramatically increasing, especially in eastern Europe.
research flow directly into the treatment of the patients
there. Physicians can call the TBinfo Service of the TTU
“Tuberculosis” at any time for advice. Advanced clinical
education courses, a national M/XDR-TB Consilium and
specific guidelines all ensure the scientific results find
their way into practice.
Tracking down antibiotic resistance
In order to better monitor the spread of M/XDR-TB and
detect the emergence of new resistance to antibiotics in
future, a laboratory unit for high-throughput analyses of
bacterial genomes has been established in Borstel. Using
ultra-modern sequencing technology, the researchers
have access to the entire bacterial genome, including the
resistance genes. This allows them to follow the propagation of the bacteria and identify chains of infection. One
breakthrough was achieved with the identification of
“outbreak strains” that are transmitted extremely often
and are already resistant to most antibiotics in eastern
Europe. An aim of the researchers is to characterise the
genetic background of the outbreak variants and discover the causes of their successful propagation. A further
aim is to map tuberculosis outbreaks in Africa and study
tuberculosis strains of the African DZIF partner institutes
– focussing on the emergence and propagation of antibiotic resistance.
To coordinate research projects with partners in Africa,
and in future in eastern Europe as well, an “International
Clinical Trials Center” has been established at the hospital
of Ludwig-Maximilians-Universität München. External
partners were gained early on to support the study of
the emergence of antibiotic resistance and its characterisation at the high-throughput analytical laboratory in
Borstel.
Furthermore, the researchers of the TTU “Tuberculosis”
are testing natural substances with the aim of developing
novel tuberculosis medicines. They have created a preclinical testing station for anti-tuberculosis substances that
simulates the conditions in the human body. The clinical
testing of these substances is a joint effort with the major
European-African trial networks.
Coordinator: Prof Dr Stefan Niemann, Borstel
Science – Translation in focus
• One in every three people in the world might be infected
with M. tuberculosis during a lifetime.
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Malaria
Science – Translation in focus
Malaria: Old challenge, new ideas
The search for a suitable vaccine against malaria continues.
Even today, it is difficult to combat malaria effectively.
Efforts often fail due to regional differences between
pathogens and their rapid adaptation. Co-infections
further complicate its treatment. Yet the biggest problem physicians are facing is the increasing resistance
to anti-malarial drugs. The TTU “Malaria” of DZIF has
been established to develop potential vaccines further
in order to allow effective immunisation of people in
malaria-endemic areas. They will also be identifying and
clinically testing novel agents against malaria. To plan
the proper therapies, researchers are also investigating
in epidemiological studies when and where malaria
pathogens appear and how they spread.
Three DZIF establishments are jointly investigating this
tropical disease: the Heidelberg University Hospital, the
Institute for tropical medicine of the University Hospital
Tübingen and the Bernhard Nocht Institute in Hamburg.
The TTU is further reinforced by intensive cooperation
with three African partner institutes in Burkina Faso, Gabon and Ghana. This gives the DZIF researchers access to
samples and data from regions in which malaria is widespread. Clinical trials on new medicines and vaccines can
also be carried out directly in endemic areas.
New vaccination method in clinical trial
One example of the TTU’s work is a clinical phase I trial
initiated in 2013 at the Institute of Tropical Medicine of
the University Hospital in Tübingen. The research team
of Dr Benjamin Mordmüller is testing the effectiveness
and safety of a new approach to malaria vaccination. The
researchers inject volunteers with viable parasites while
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In the spring of 2013, the Tübingen group had already
been involved in the preparation of another clinical trial
at the partner site, the Albert Schweitzer Hospital in Lambaréné, Gabon. Using the human malaria infection model
established within DZIF, the importance of the sickle-cell
gene and acquired immunity is being investigated.
Mathematics for better predictive models
In order to widen the possibilities for statistical evaluation and modelling of research data, the research group
“Mathematical Modelling and Biostatistics” was established at the Bernhard Nocht Institute. Here, scientists
are creating mathematical models to describe the appearance and lifecycle of parasites in the blood of infected
people as well as the development of the pathogens in the
human body. These models will also allow them to analyse
seasonal and geographical fluctuations in the spread of
the parasites and thereby better estimate the frequency
of illness.
• Malaria occurs mainly in tropical regions.
• It is widespread in most of sub-Saharan Africa where
the incidence rate and mortality is especially high in
children.
• According to the WHO, in 2012 approximately
627,000 people died from malaria and 207 million
were infected worldwide.
• The malaria pathogens (plasmodium parasites) are
transmitted to people by mosquitoes.
In Heidelberg, further projects of this TTU are focussing on how the immune system of infected volunteers
responds to infection, and on the development of novel
drugs against malaria. With the help of molecular diagnostic techniques, the TTU is also investigating how often
African children suffer from malaria co-infections, how
greatly they are at risk and how these infections can be
treated.
Coordinator: Prof Dr Peter Kremsner, Tübingen
Science – Translation in focus
simultaneously administering an anti-malarial that weakens the plasmodia. The desired result is lasting immunisation. “Because conventional preventative approaches
are so far disappointing, we are testing new, at first sight
astonishing methods,” Mordmüller says.
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HIV
Science – Translation in focus
New approaches to controlling
and healing HIV infection
Both a physician and a researcher: Dr Jörg Janne Vehreschild at the intensive care unit of the University Hospital Cologne.
Around 30 years after the discovery of HIV as the cause
of the immunodeficiency disease AIDS, present-day
researchers must focus on the prevention of new HIV
infections, the medical treatment of HIV patients, and
the healing of HIV infections. These are the focuses of
the TTU “HIV” of DZIF.
Cutting HIV out of the host genome
HIV is a retrovirus. When it infects a cell it must make
sure the newly infected cell transcribes the virus’s genetic
material, consisting of RNA, into DNA and then integrates
it stably into the host cell’s own chromosomal DNA. Successful integration is crucial for infection; the integrated
viral RNA can then lead to the production of new viruses
or remain latent over a very long time.
As yet little is known about the laws governing HIV’s integration into human DNA. The TTU “HIV” is studying this
issue intensively. The DZIF researchers want to understand how and where the host cell integrates the foreign
DNA, how the foreign sequences are read and how,
under certain circumstances, it is muted and therefore
remains latent over several years before suddenly being
reactivated to new virus production. This will lead to ways
in which to eliminate latent viruses.
The viral DNA in the host cell’s chromosome is the target
of a new strategy for eliminating latent infections. The
researchers are attempting to cut out the viral genome
using a modified form of the enzyme Tre recombinase,
which specifically recognises HIV sequences. In this
project, involving the Heinrich Pette Institute, the
University Medical Center Hamburg-Eppendorf and
Heidelberg University, the scientists have developed a
genetic engineering technique by which to produce this
Tre recombinase in stem cells. “We are currently verifying
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• Worldwide 34 million people are infected with HIV,
70 percent of them in sub-Saharan Africa.
• The number of AIDS fatalities is dropping each year,
but the incidence of new infections is as high as ever.
• Vaccination and complete healing are so far
impossible.
• HIV is extremely genetically variable and can remain
latent inside infected cells for a very long time.
• Primary goals: prevent, treat and ideally heal HIV
infection.
the effectiveness with which Tre recombinase cuts the
viral DNA out of the host genome,” says Prof Hans-Georg
Kräusslich, coordinator of the “HIV” TTU.
Systematically documenting patient data
In the mid 1990s, after the discovery of HIV, drugs that
suppress reproduction of the virus were developed.
While these drugs help the patients, they often have
strong side-effects. They can lead to organ damage in the
long term, and the virus may become resistant to them.
Reliable recommendations depend on documentation
of the highest quality. Only by standardised observation
over several years can important causal relationships be
established. In many cases, the reasons for treatment failure or adverse events remain unclear. Additionally, basic
researchers need information and biological samples if
they are to identify the causes.
The TTU “HIV” began setting up a scientific platform for
these purposes in 2013. A junior group led by Dr Jörg
Janne Vehreschild with a methodical and medical informatics focus was initiated at University Hospital Cologne.
One of the first duties of this group was requirements pl-
anning with the partners of the “HIV” TTU. In collaboration with the Robert Koch Institute, a common IT solution
is now being implemented at all locations. This makes it
possible to document patient data systematically. These
data can then be transmitted between centers and
international partners in standardised form. Furthermore, biomaterial – such as tissue samples or biopsies – can
be recorded with the storage location and a link to the
clinical record. “For our collaboration in the TTU to be a
success, it is decisive for us to gain and exchange harmonised data and sample material,” Vehreschild says. “For
this, we have successfully developed a common ethics
and data safety concept for all locations.”
Coordinator: Prof Dr Hans-Georg Kräusslich,
Heidelberg
Science – Translation in focus
• Effective antiretroviral therapies are increasingly
available.
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Hepatitis
Science – Translation in focus
Focusing on improving therapy
Optimism in the fight against hepatitis B: Prof Ulrike Protzer and Dr Jan-Hendrik Bockmann.
Researchers of the TTU “Hepatitis” want to improve the
prophylaxis against chronic viral hepatitis and develop
therapies to cure it. They intend to explain the role of
resistance to antiviral drugs, and to identify novel targets
for the development of improved drugs.
The available antiviral drugs cannot cure hepatitis B. If
treatment is interrupted, then hepatitis B reactivates. The
template for hepatitis B virus replication is the so-called
“cccDNA”. This is a stable circular DNA form which the
virus deposits in the nucleus of infected liver cells to persist.
Molecular mechanism to eliminate cccDNA discovered
Under the umbrella of DZIF, scientists working with Prof
Ulrike Protzer and Prof Mathias Heikenwälder of Technische Universität München and Helmholtz Zentrum München, together with national and international partners,
have discovered how the viral cccDNA can be eliminated.
The researchers showed that, after administering inter-
feron-α, expression of the enzyme APOBEC3A is induced
in the infected liver cells. This enzyme cuts amine groups
out of the cytosine bases of the nuclear cccDNA, thereby
initiating its degradation. The same effect can be achieved
by activating the lymphotoxin-ß receptors to stimulate
expression of the deaminase APOBEC3B. The genome
of the liver cells remains unaffected. “The activation of
deaminases is an interesting starting point for developing
new therapies that allow us to cure hepatitis B,” explains
Ulrike Protzer.
Mode-of-action of cyclophilin antagonists identified
To reproduce its RNA genome, the hepatitis C virus is dependent on proteins from liver cells. For example, binding
of the cellular protein cyclophilin A to the viral protein
NS5A promotes replication of the viral genome. Cyclosporine derivatives that inhibit cyclophilin are potential candidates for new antiviral drugs. These are currently being
tested in clinical trials.
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Other focuses
The active agent Myrcludex-B developed by DZIF researcher Prof Stephan Urban is currently in clinical trials. It
binds to the cellular receptor for hepatitis B viruses and
thus blocks the spread of viruses in the liver. In the mouse
model, it helps control the virus. Initial trials in patients are
being initiated with the help of DZIF.
With broad-based epidemiological studies, the TTU “Hepatitis” intends to define the therapeutic need in Germany
and to make treatment options accessible to patients. In
addition, the TTU is searching for biomarkers that will
allow prediction of the course of the disease, successful
treatment and finally the chance of a cure. It is furthermore striving to improve the infrastructure for creating
patient cohorts and for supporting clinical trials.
Coordinator: Prof Dr Michael Manns, Hannover
• Viral hepatitis (liver inflammation) is caused by the
hepatitis viruses A to E.
• Hepatitis A and E viruses are transmitted mainly
through water and food contaminated with infectious faeces; hepatitis B, C and D viruses are typically
transmitted by direct blood contact or – mainly in
the case of hepatitis B virus – through sexual contact.
• Around half a billion people in the world, one million
in Germany, are chronically infected with hepatitis B,
C and D viruses. They are at high risk of developing
liver cirrhosis or hepatocellular carcinoma; more than
one million humans die from this each year.
• Vaccines exist for hepatitis A and hepatitis B, but not
for hepatitis C or hepatitis E.
Science – Translation in focus
A research group working with DZIF scientist Prof Ralf
Bartenschlager of the Heidelberg University Hospital
has shown that cyclophilin-A inhibitors effectively block
reproduction of the hepatitis C virus genome by inhibiting
the formation of new virus-induced membrane vesicles
in infected cells. These membrane vesicles provide the
essential scaffold for the coordinated sequence of viral
reproduction steps, and serve to protect the viral RNA
against RNA-degrading cellular enzymes. The antiviral
action of cyclophilin antagonists is directly dependent on
the viral protein NS5A. If cyclophilin is sequestered by the
inhibitors, then NS5A is unlikely to fold correctly and, consequently, no membrane vesicles will form. “With that, we
have discovered a new principle of antiviral therapy. Also,
compared to direct NS5A inhibitors, therapy resistance
to cyclophilin inhibitors is much less likely to develop,”
Bartenschlager says.
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Gastrointestinal Infections
Science – Translation in focus
New drugs against
gastrointestinal microbes
Patient samples arrive at the microbiological laboratories of Hannover Medical School.
With the TTU “Gastrointestinal Infections”, DZIF
intends to improve the diagnosis, treatment and prevention of gastrointestinal infections. The scientists in
Braunschweig, Hannover, Munich, Tübingen, Cologne
and Münster are interested in bacterial pathogens such
as EHEC, Helicobacter pylori and salmonellae. The researchers are aiming at novel therapy strategies targeted
against a specific bacterium or group of germs. This will
ensure only pathogens are attacked and not the natural organisms in the digestive tract, as is the case with
existing therapies.
The bacterium Helicobacter pylori is a dangerous microorganism. Every second person carries it. Many people
contract stomach ulcers or even stomach cancer from
this infection. The possibilities for treatment are limited
and there are no vaccines against the bacterium so far.
A project of Technische Universität München in collaboration with Hannover Medical School has made significant
progress. The group led by Munich microbiologist Prof
Markus Gerhard is preparing a clinical phase I trial for a
vaccine against H. pylori. If it succeeds and is approved it
will be the first vaccine against this bacterium. The advantage of this is that, until now, most patients who have fallen
ill from H. pylori have been treated with antibiotics. Such
treatment is difficult and is also losing its potency because
strains of the pathogen are becoming resistant.
Helicobacter vaccine within reach
The new vaccine contains essential components of the
bacterium complemented with an adjuvant – a substance
that boosts the immune system’s defensive response.
Now that the vaccine has been tested in mice and monkeys, the scientists intend to test its effectiveness and
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Analysis of the gut flora pays off
Another focus of the TTU is therefore to research new
therapeutic approaches against pathogenic gut microbes
in consideration of the natural gut flora. Digestion in the
stomach and intestine only works thanks to the countless beneficial bacteria that live there. Scientists call the
entirety of GI microbes the microbiota; it is of enormous
importance to our health. The TTU researchers are
looking to use specific molecular and genetic traits of the
microbiota as biomarkers to improve our understanding
of bacterial gastrointestinal infections, and to develop
individual treatments against them. As of autumn 2013,
they have been building a cohort of patients whose gut
flora has been analysed multiple times during their time
in hospital. This will allow the researchers to detect
biomarkers that indicate, for example, an elevated risk of
infection with Clostridium difficile – the bacterium considered the most significant cause of diarrhoea infections
in hospitals. The preparations for recruiting suitable
patients and for testing and evaluating samples have been
concluded. At the end of 2013, the cohort comprised
around 200 patients and the study will eventually include
up to 2000 patients in total.
In other projects of this TTU, a Germany-wide active
centre is being established for fundamental research into
the microbiome. Medical professionals at the University
of Tübingen and Ludwig-Maximilians-Universität München are developing new animal models, for instance, by
which innovative treatment strategies can be tested very
reliably at a preclinical stage.
Coordinator: Prof Dr Sebastian Suerbaum, Hannover
Science – Translation in focus
safety in people. In preparation for the clinical trial, they
have set up test systems for the vaccine and analysed
the diversity of the antigens present in the vaccine. The
results look good for the success of the clinical trial – and
with it for an important step forward in the fight against
this dangerous gastric germ.
• E
very year, more than three million people worldwide
die from infectious gastrointestinal diseases.
• At greatest risk are children and people with a weakened immune system.
• Helicobacter pylori is found in 50 percent of the
world’s population and can cause stomach ulcers
and stomach cancer.
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Infections of the immunocompromised Host
Science – Translation in focus
Protecting transplant patients
against infections
Researchers at TU München search for immune cells with a “good memory”.
It is a serious problem in hospitals. For immunocompromised patients, pathogens that are normally harmless
can suddenly become a life-threatening danger. The reasons for this increased susceptibility and the various possibilities for protecting these patients are being studied
within DZIF at several locations. The TTU “Infections of
the immunocompromised Host” is a platform on which
the expertise of the individual groups is being bundled
and their activities intensified.
DZIF researchers are investigating at several locations
– Munich, Hannover-Braunschweig, Heidelberg and
Tübingen – what molecular, cellular and/or genetic causes
underlie the increased susceptibility to infections of immunocompromised patients. They aim to identify biomarkers by which they can better estimate the individual risk
of infection, and to develop novel drugs and treatment
methods in order to transfer this knowledge from bench
to bedside.
DZIF transplant cohort formed
In 2013, the DZIF scientists initiated a core project of
the TTU: a one-of-a-kind transplant cohort in Germany.
The DZIF Transplant Cohort includes patients who have
received a donor organ or who have received haematopoietic stem cell transplantation (HSCT). The researchers
will be collecting and analysing medical data and biological
samples from these patients over a long period.
Background: After a transplantation, patients often
depend for the rest of their lives on medication in order to
prevent rejection responses. However, these drugs make
T-cells against infection
Scientists led by Prof Dirk Busch of Technische Universität München are investigating how to reduce the risk of
infection in patients after HSCT. “We are concentrating on
infections with pathogens that can reside permanently in
healthy people,” says Busch. “In the case of immunodeficiency, these pathogens can be reactivated and cause severe symptoms.” Some examples are herpes viruses such
as cytomegalovirus and Epstein-Barr virus. The scientists’
intention is to treat patients by giving them specific immune cells that actively attack these pathogens. The method
is called adoptive cell therapy.
• People with a weakened immune system are at especially high risk of infection with viruses, bacteria, fungi
or parasites.
• At particulary high risk are transplant patients, the
chronically ill, people with hereditary or acquired
immunodeficiencies and the elderly.
• They require special medication because conventional antiinfectives often do not help.
the patients more susceptible to infection. The problem is
far from new, but there are many questions still unanswered. For instance, what differences exist between individual patients regarding susceptibility, and how do certain
infections affect the long-term success of the transplant
and the patient’s survival.
So far, the organisational basis has established for effective collaboration between the transplant clinics and
scientific institutes involved. Furthermore, an Ethical and
Privacy Policy and a protocol for collecting samples in
biobanks have been established.
The cells administered are called T-lymphocytes, or T-cells
for short. They search the body for pathogens and, after
specific detection, can eliminate infected cells. In various
subprojects, the researchers are working on characterising different sorts of T-cells and their activity in greater
detail. An important result in 2013 was the discovery that
so-called central memory T-cells (TCM) are especially
suitable for adoptive cell therapy, requiring administration
of just a few cells. Now the researchers intend to develop
methods for treating patients with these cells.
After promising preclinical work, the new method of TCM
transfer will soon be tested clinically for infection prophylaxis in patients after HSCT. As soon as all regulatory
requirements have been approved (probably by the end
of 2014), the first patients will receive purified donor-derived TCMs as part of a DZIF-funded clincal trial. These
cells are expected to protect against a variety of different
pathogens. The researchers obtain them from healthy
stem cell donors by a newly developed method. The main
goal of the trial is to demonstrate the clinical safety of
the novel approach, as well as to obtain first insights into
clinical efficacy.
Coordinator: Prof Dr Dirk Busch, Munich
Science – Translation in focus
19
20
Healthcare-associated and Antibiotic-resistant bacterial Infections
Science – Translation in focus
New agents and therapies should
curb healthcare-associated infections
Controlled use: Is using less antibiotics the key to reducing resistance?
Better hygiene, more targeted use of antibiotics and
novel active agents are important in the fight against
healthcare-associated infections. Despite these measures, the number of patients affected remains as high as
ever. The biggest problems are presented by methicillin-resistant Staphylococcus aureus (MRSA) strains
and by enterobacteria that produce extended-spectrum beta-lactamase (ESBL) enzymes that render
the group of beta-lactam antibiotics ineffective. So
far, too little is known about the causes and possible
countermeasures. Also, there is a lack of clinical trials
for testing new active agents. The TTU “Healthcare-associated and Antibiotic-resistant bacterial Infections”
closes these gaps.
The development of resistance of microorganisms is inextricably linked to the use of antibiotics. In a multicentre
trial, a group led by Prof Harald Seifert of the University
of Cologne is investigating to what extent the introduction
of an antibiotic stewardship programme would lower the
consumption of antibiotics and, with it, the frequency of
healthcare-associated infections caused by antibioticresistant bacteria. “Especially in times when the development of new antibiotics is floundering, careful use of
antibiotics is of critical importance both in the field of
ambulant medicine and in hospitals,” Seifert explains.
Handling insidious enterobacteria
Patients undergoing chemotherapy are at especially high
risk of infection. ESBL-producing enterobacteria in the
gut can cause severe septicaemia in these patients. In two
trials led by PD Dr Maria Vehreschild of DZIF Bonn-Cologne, DZIF researchers are studying how to curb these
often highly stubborn infections. One possible approach
21
• The pathogens most frequently cause wound infections,
urinary tract infections, pneumonia or septicaemia.
• Treatment is becoming more difficult as many of the
bacteria and fungi become multiresistant, in other
words immune, to common antibiotics.
• While these pathogens are only rarely a problem for
healthy people, they can present a considerable danger
for seriously ill, immunocompromised patients.
is to take isolation measures: “So far, it is unclear to what
extent isolation, which is highly costly and stressful for the
patient, prevents transmission between patients,” explains Prof Oliver Cornely. The researchers are also testing
treatment with non-absorbable antibiotics to eliminate
ESBL-producing enterobacteria from the gut.
“We are now producing new variants of these designer
phage proteins and testing their action in comparison to
mupirocin, the normal choice of antibiotic for treating staphylococci from the nasal mucosa,” Peschel explains. “By
the end, we hope to have developed at least one phage
lysin to sufficient maturity for testing in clinical trials.”
Designer phage proteins
In a collaborative project of the University of Tübingen,
the University of Münster and biotech firm Hyglos in
Bernried, a group led by TTU coordinator Prof Andreas
Peschel (Tübingen) is investigating the possibilities of using
novel antibacterial agents derived from bacteriophages.
Bacteriophages are viruses that specifically infect bacteria
and then lyse them from the inside out using proteins.
As in Cologne, enterobacteria are the focus of another
project at Gießen University. Researchers there are
currently characterising the genome of these germs. In
future, it should be possible to detect especially dangerous strains early on and prevent them from spreading.
Furthermore, at the University Hospital Tübingen, Prof
Evelina Tacconelli has been appointed professor of infectiology disease, creating a local platform for clinical trials.
The idea is to use the high specificity and bactericidal
action of phages to eliminate S. aureus effectively without
disrupting the human microflora. Certain phage lysin
proteins shall be produced and used to attack resistant
Staphylococcus aureus bacteria directly at their site of origin in the nasal mucosa. One phage protein studied in an
initial set of trials acts highly specifically against S. aureus
as hoped.
Coordinator: Prof Dr Andreas Peschel, Tübingen
Science – Translation in focus
• Nosocomial infections – those contracted in hospitals
– are caused in most cases by bacteria or fungi, and in
rare cases by viruses.
22
Novel Antiinfectives
Science – Translation in focus
Activating silent reserves
Focus on defence: an activated immune system fights even concealed pathogens.
Drugs against bacterial or viral pathogens are hardly
blockbusters – only a handful of antiinfective preparations generate a billion-dollar annual turnover. Their relatively meek economic presence is in contrast to their
medical importance. Without novel antiinfectives, patients infected with resistant germs could find themselves without any options for therapy while advanced and
intensive medicine would quickly reach their limits. The
TTU “Novel Antiinfectives” of DZIF gives impetus to the
development of these urgently-needed new drugs.
Since life began, infectious pathogens have been an
ever-present threat. A refined system of immunosensory receptors is capable of detecting the intrusion of
pathogens early and, in most cases, manages to activate
immunological defence mechanisms that can prevent the
pathogens from spreading before an infection becomes
manifest. “Toll-like receptors” (TLRs) and “retinoic acid
inducible gene I helicases” (RLHs) are of pivotal importance in this detection. They are located in the membranes or cytoplasm of immune cells and somatic cells, where
they recognise characteristic nucleic acid structures of
bacteria or viruses and can quickly activate our innate
defence system. However, those pathogens that do cause
manifest infectious diseases have done so by developing
mechanisms to trick and subvert the host’s immunosensory detection system. DZIF scientists have now identified compounds based on synthetic, short-chain nucleic
acids (oligonucleotides) that specifically bind to and
activate TLRs and RLHs. These can be used to therapeutically activate the host’s highly effective innate defence
mechanisms. Then even pathogenic organisms that can
“hide” from the immune detection system can no longer
propagate. Prof Gunther Hartmann of the University
Hospital Bonn reports: “We were able to demonstrate
in a series of animal models that these oligonucleotide
23
Clinical use still a long way off
Extensive preparations need to be made before the oligonucleotide ligands can be tested in humans. “We want to
optimise the molecular architecture of the ligands so that
they bind highly specifically and thereby direct the host’s
innate immune defences even more effectively against
bacteria and viruses,” Hartmann explains. “Our aim is to
complement the classic antiinfectives, such as antibiotics,
with the body’s natural defence mechanisms, in order to
expand the antiinfective therapy spectrum and make life
hard for the rising number of antibiotic-resistant germs.”
Using silent genes for drug production
Some parts of microorganism DNA are only transcribed
into proteins under certain environmental conditions; at
all other times these DNA regions remain “silent”. From
analysing microbial genomes, it turns out that certain
bacteria have many silent gene clusters that encode the
synthesis of active compounds. Researchers in the TTU
“Novel Antiinfectives” are activating such DNA regions
and testing whether their products are useful for the
treatment of infections. To this end, researchers working
with Dr Tilmann Weber of the University of Tübingen have
developed a new bioinformatics platform (antiSMASH)
that can be used to track down such gene clusters (genome
mining), and which also makes suggestions as to the planar
structure of the corresponding compound. “After we used
this to identify and activate silent gene clusters, we were
actually able to isolate and characterise a promising class
of compounds,” Weber reports. Other substances from
the class of glycopeptides were already known but, after
activating the silent gene clusters, they can be produced
at much higher yields and therefore at much lower cost
than before.
Coordinator: Prof Dr Hans-Georg Sahl, Bonn
• Antibiotics are still our most important weapon in the
fight against infections.
• Without antibiotics, modern advanced medicine
would be inconceivable.
• Bacteria are becoming increasingly resistant to
antibiotics.
• The number of new candidate agents in pharmaceutical research departments is small.
• For many years now, too few innovative antiinfective
drugs have come onto the market.
Science – Translation in focus
ligands have outstanding properties for preventive or
therapeutic use against infectious disease. This approach
is already in preclinical development and will later be
tested in clinical trials.”
24
Product Development Unit
Research infrastructures
Advice for the step into
a new world
DZIF promotes collaboration between research and the pharmaceutical industry.
The path from a promising scientific discovery to development of a drug or vaccine is long and laborious. After
positive research results are achieved, many years elapse
before a new medicine or method of treatment is approved – and the abandonment rate is high. To improve the
translation of scientific findings into medical products,
DZIF has established the TI “Product Development
Unit” (PDU). It combines the expertise of two offices: the
Office for Scientific and Regulatory Advice of the Paul
Ehrlich Institute in Langen and the Translational Project
Management Office of the Helmholtz Centre for Infection Research in Braunschweig.
Their activities include advising project heads and their
teams on the scientific, regulatory and organisational aspects of product development. In collaboration with the
project teams, experts in the translational infrastructure
PDU draft funding applications, design product profiles
and create development and utilisation plans which are
then jointly implemented. The regulatory requisites for
the developmental projects are identified and suggestions for realistic solutions developed. The advisors help
identify potential industrial partners for joint studies and
the subsequent exploitation of acquired property rights.
Many consultation meetings were held in 2013 and the
experience gained through them was preserved in a
database. This will make it easier in future to recognise
and overcome hurdles blocking the path to the development of active agents and drugs. For this it is important to
include the PDU in the earliest possible product developmental phase. The DZIF unit also provides seminars
on special aspects of product development. In 2013, for
example, a seminar was held at the Paul Ehrlich Institute
on “Due Diligence”, the investigation of a promising development by a buyer such as “Big Pharma”.
Coordinator: Prof Dr Klaus Cichutek, Langen
25
Clinical Trial Unit
Fostering competitively viable, efficient and high-quality standard ID clinical trials at all DZIF sites is the main objective.
The experts of the TI “Clinical Trial Unit” (DZIF-CTU) are
fostering the transfer of findings from basic and clinical
research into therapeutic applications. DZIF’s nine specialised infectious disease (ID) clinical trial units (CTUs)
provide the platform for testing and evaluating novel
clinical compounds and medicinal products within DZIF.
The DZIF-CTU Coordinating Office (CO) at the Centre
for Clinical Trials, Cologne, forwards feasibility requests
to the associated CTUs, coordinates and supports the
implementation of a mutual quality management system
and manages the centralised, web-based site management system. The CO also supports the CTUs on all
matters of conducting clinical trials.
The main objective of this TI is enabling competitively
viable and efficient performance of ID clinical trials at all
DZIF-sites following uniformly high quality standards.
This applies to trials with compounds and medicinal products developed within DZIF and to industry-sponsored
trials. “In the long term, we want to establish DZIF as pre-
ferred partner for international academic and industrysponsored trials,” states coordinator Prof Oliver Cornely.
In 2013 the Coordinating Office introduced a mutual
quality management strategy at all DZIF CTUs entailing
the implementation of the BMBF-sponsored standard
operating procedure templates.
“Furthermore, we want to highlight DZIF-CTU´s excellence and visibility in an international setting,” Cornely
adds. The CO successfully integrated the DZIF-CTU
network in three calls of the European Union (IMI-JU
Calls “COMBACTE”, “APC”, and “CARE”), making it part
of an international network of clinical trial sites and microbiological laboratories. Within these networks the CTUs
will participate in clinical trials focussing on bacterial
resistance in collaboration with the industrial partners
GlaxoSmithKline, MedImmune and AstraZeneca.
Coordinator: Prof Dr Oliver Cornely, Cologne
Research infrastructures
Collaboration with universities
and industry
26
African Partner Sites
Research infrastructures
Helpful partnership
Joint projects with established African partner institutes.
Many infectious diseases that appear only rarely in
Central Europe are endemic and widespread in African
countries. Improved collaboration with scientists in Africa
is therefore vital if we are to research and effectively
combat these diseases. In the TI “African Partner Sites”,
DZIF will be intensifying this cooperation by strengthening relationships, some of them long-standing, between
various DZIF locations and partners in Africa, as well as
coordinating their activities more efficiently.
One primary goal is to establish a network between
DZIF’s institutes and four established scientific institutions in Ghana, Gabon, Burkina Faso and Tanzania for the
purpose of jointly researching malaria, tuberculosis, HIV
and so-called neglected diseases. German and African
experts are jointly analysing the spread of these diseases
– and thereby creating the basis for a better understanding of the pathogens. All findings flow into a database
and are thus available to all DZIF researchers. An advantage of this infrastructural unit is that the four partner
establishments are located in different areas of Africa,
with different environmental conditions and different
hereditary risk factors in the population.
One current focus of the TI is a two-year project on fever
without source (FWS). Every year, around 200 to 300
children with this symptom are admitted into the study
at the hospitals of the four partner institutes. The pilot
phase of the project has been concluded successfully and
the actual FWS study has already started. Its results will
broaden our view on the spectrum of infectious germs in
Africa – which will allow us to detect emerging infections
more quickly in future.
Coordinator: Prof Dr Jürgen May, Hamburg
27
Natural Compound Library
A library of bacteria and fungi is to be made available to all DZIF units.
Not all microorganisms make us sick; many are even our
allies in the fight against infectious disease. They produce
a diversity of substances that inhibit the effects of pathogenic germs on the organism. As a result most antibiotics
are made from substances of natural origin. Yet only a few
of the countless suitable natural compounds have been
researched for their medical usefulness. With the TI “Natural Compound Library”, DZIF has intensified and restructured its research in this field – and is building upon the
experience and technical facilities at the Helmholtz Centre
for Infection Research (HZI), the Helmholtz Institute for
Pharmaceutical Research Saarland (HIPS) and the Leibniz
Institute DSMZ (German Collection of Microorganisms and
Cell Cultures).
The aim is to extend the HZI’s existing library of bacteria
and fungi and their active compounds, and to make it available to all units of DZIF for antibiotic research and screening.
In addition, the natural compound samples will be analysed
at the HZI in novel test systems developed by the Department of Chemical Biology.
The scientists have obtained numerous natural compounds,
predominantly from myxobacteria, which are now being
studied in greater detail. One of the groups of chemical
compounds is known as the cystobactamides . These compounds exhibit a broad spectrum of anti-infectious actions
which are to be analysed and evaluated in a follow-up
project within the TTU “Novel Anti-Infectives”.
Since 2013, the scientists have also renewed their focus
on fungi. Fungi are an excellent and diverse source of novel
antibiotics. The first extracts from these organisms were
recently made available within the DZIF network for searching for active compounds. Further interesting samples
are expected in 2014, for example extracts from acidobacteria that have been processed at the DSMZ.
In the search for potential natural antibiotics, methods employed by researchers of this TI include functional genomics
and systems biology. Existing production facilities have
been stocked up in order to produce promising substances
in ample quantities. As one example, myxobacteria can
now be obtained at HZI in fermentation tanks of around
2000-litre capacity.
Coordinator: Prof Dr Rolf Müller, Braunschweig/
Saarbrücken
Research infrastructures
Using bacteria and fungi
to fight infection
28
Biobanking
Research infrastructures
Expanding infrastructure
and collections
Biobank standards are being established for the biomaterial collections of the DZIF institutes.
At its institutes in Heidelberg, Munich and HannoverBraunschweig, DZIF is building a platform for biobanks
and biobanking technologies. Their focus lies on the
standardised recording and quality control of biomaterials as well as novel technologies for entry, storage and
processing. “This allows a broad, multi-location use of
reliable and comparable samples for basic research and
translational research within DZIF,” explains Prof Peter
Schirmacher, coordinator of the TI “Biobanking”.
Quality-assured collections of tissue samples, liquid
samples, infectious pathogens and microbial compound
producers are already established at the selected locations. The biobank in Heidelberg collects infectious
tissue, which is entered into the records and stored using
2D barcodes. Scanning this code allows rapid, qualityassured recording and traceability of the samples.
The German Collection of Microorganisms and Cell
Cultures in Braunschweig has expanded its stock of
microorganisms. Samples of the gastroenteritis-causing
bacterium Clostridium difficile and more than 60 isolates
of intestinal bacteria of mice have been recorded and
analysed.
The TI “Biobanking” has developed an ethics and privacy
policy and expanded the international relationships of
DZIF (Infectious Diseases Biobank, London). The infrastructure meeting in Braunschweig largely initiated and
organised by the TI served to intensify the collaboration
with the other TIs and TTUs. Furthermore, the TI initiated collaboration with the biobank platforms of other
German Health Research Centres and coordinated the
meetings that were held.
Coordinator: Prof Dr Peter Schirmacher, Heidelberg
The Munich team has developed a biobank catalogue,
following the European model, for documenting the
biomaterial collections of the DZIF institutes. So far, 29
biobanks are registered in this catalogue. For DZIF’s
transplant cohort, a separate register database has been
set up for the data of patients at risk of infection.
29
Bioinformatics
Bioinformatic methods are indispensable in infection research.
Technological advances are ushering in a new era of
clinical microbial diagnostics and epidemiological tracing
of outbreaks. The genomes of both pathogens and hosts,
and the active genes coded within them, can now be
fully sequenced within a day. Yet routine use of microbial
sequencing in clinics and public health establishments is
still a long way off. There is a lack of automated analytical
tools for converting the enormous quantities of sequencing data into information that can be translated into new,
improved treatment strategies. To exploit bioinformatics
fully, researchers need powerful hardware and software
tailored to the specific problems as well as skill in handling
the bioinformatic tools.
To grant all DZIF researchers access to a uniform computing environment with powerful hardware and interpretation pipelines for sequence data, the TI “Bioinformatics”
was established. Participants include Gießen University
and the Helmholtz Centre for Infection Research in
Braunschweig.
DZIF Bioinformatics is dedicated to three service areas.
These are information transfer, training activities and
the establishment of a “Bioinformatics Resource Cen-
tre” (BRC). Synergy effects will be exploited to pass on
the existing bioinformatics expertise to partners and
to support the DZIF researchers with training courses.
Since the establishment of the BRC in 2013, enormous
quantities of data can be rapidly and reliably prepared and
analysed. The platform www.bioinformatics-platform.
dzif.de offers clinicians and associated scientists automated analysis programs: for comparative genomics,
mutation analysis, metagenomics and diversity analyses
of microbial communities, analyses of host genome and
transcriptome datasets, and the illustration of genetic
relationships between gene regulatory networks and
metabolic pathways. Workshops and training courses
have also been held to familiarize DZIF researchers with
the new tools.
The TI “Bioinformatics” thereby supports the establishment of sequencing in hospitals. This benefits the patient,
with the new tools helping to control outbreaks of pathogens and providing a rational basis for curbing antibiotic
resistance.
Coordinators: Prof Dr Trinad Chakraborty, Gießen;
Prof Dr Alice McHardy, Braunschweig
Research infrastructures
Tracking infections
with informatics
30
DZIF Academy
Promotion of young researchers
Fast track for talented students
The next generation will finally close the divide between research and clinical practice.
Dr Jan-Hendrik Bockmann is a physician and researcher
by conviction, yet combining daily hospital work with
research is no easy task. “Work at the hospital takes up a
lot of your time,” he says. Accordingly, time for research
is limited. Bockmann therefore applied for a stipend from
the DZIF Academy. It offers clinical physicians the opportunity to advance their career in infection research.
part-time, and has extended eleven more by half a year.
“This shows how extensive the fellows’ projects are,” says
Cauleen Noël, contact person for the DZIF Academy. The
Academy also assists young mothers wishing to return to a
research career by awarding maternity stipends covering
a large portion of their salary. Three such stipends started
at different locations in 2013.
“To apply, you need to find a partner institute within DZIF
and work out a draft for a project that you would like to
conduct there for one year,” Bockmann recounts. He
opted for the Institute of Virology at the Technische Universität München, where he found the ideal conditions for
doing research on the hepatitis virus under the direction
of Prof Ulrike Protzer. The physician from Hamburg feels
the DZIF Clinical Leave Stipend perfectly answers and
justifies his wish to concentrate more deeply on research.
“I’ve been integrated into a team of scientific colleagues
that fosters an active and stimulating exchange of results
and ideas,” he comments enthusiastically.
The Academy’s aim is to get young scientists interested
in infection research and to enrich this discipline with
knowledge direct from hospitals. To this end, students
are invited to enrol in doctoral programmes; in spring and
autumn schools focussing on scientific or clinical topics, researchers and physicians can also deepen their knowledge
and exchange expertise.
Since the beginning of 2013, DZIF has awarded seven
Clinical Leave Stipends, of which five are full-time and two
Jan-Hendrik Bockmann already benefits from the Academy. He will be following a two-track career in the future
with a double benefit. While practicing as a physician back
in Hamburg, he will be able to build upon the latest insights from research. As a researcher, his experience from
medical practice will be a continual source of inspiration.
31
Collaboration in DZIF
Countless samples serve the research community.
When monitoring the emergence of new infectious
diseases, it is of immeasurable value to understand the
evolutionary development of pathogens in detail. Only
with this knowledge can predictions be made on the
potential dangers from new infectious viruses or bacteria, and preventive methods and treatments developed.
Within DZIF, scientists from basic research, diagnostics
and clinical research get together to work on such acute
topics of great importance to our health. One prominent
example: In 2013, DZIF researchers of the TTUs “Emerging Infections” and “Hepatitis” discovered a virus in tentmaking bats that is closely related to the hepatitis B virus.
It is also capable of infecting humans – but conventional
vaccines will not protect against it. These early warning
signs are very important because hepatitis B is one of the
most widespread infectious diseases of all. It can lead to
liver inflammation and cancer.
To study this virus, virologists of the TTU “Emerging
Infections” at the University Hospital Bonn, members of
the TTU “Hepatitis” at Gießen University and researchers
from other countries took blood and liver samples from
thousands of bats of numerous species from Panama,
Brazil, Gabon, Ghana, Papua New Guinea, Australia and
Germany. They tested these for viral DNA of the hepatitis
B virus and discovered three different virus strains that
are very similar to the human hepatitis B virus. They also
discovered that one virus, isolated from the tent-making
bat, can infect human liver cells. This was not the case with
the other two virus strains.
Further tests on this virus, which could be infectious to
humans, revealed that the standard vaccination against
hepatitis B used around the world does not protect
against the virus from the tent-making bat. “This changes a
fundamental belief,” says Prof Christian Drosten, Director
of the Institute of Virology at University Hospital Bonn.
“The question now is whether it will be possible to eradicate hepatitis B worldwide using the conventional vaccine.” PD Dr Dieter Glebe of the National Reference Centre
for Hepatitis B and D Viruses adds: “The discovery of new
hepatitis B viruses from bats should be a starting point for
developing more effective hepatitis B vaccines.”
Collaboration in DZIF
On the trail of the hepatitis B virus
32
DZIF Highlights 2013
DZIF Highlights 2013
Step by step against infections
DZIF supports
the fifth bi-annual
meeting of the Global
Virus Network, hosted at
Technische Universität München under the leadership
of Prof Ulrike Protzer.
International
cooperation in the
DZIF Biobank: A Memorandum of Understanding is
signed with the Infectious
Diseases Biobank
London.
July
DZIF scientists from the Research
Center Borstel and Klinikum der Universität München evaluate the Marius
Nasta Institute in Bucharest, a new
potential DZIF clinical trial unit in
eastern Europe.
June
Retreat: In June, the DZIF partners
get together at Lake Tegernsee to
decide their strategy for the future.
The Scientific Advisory Board
meets for the first time.
January
March
DZIF researchers
explain how killer
T-cells multiply. The
scientists publish
their results in the
journal “Science”.
In the scope of the European “Innovative
Medicines Initiative – Joint Undertaking”
(IMI-JU), the network project COMBACTE
starts. COMBACTE plans clinical trials to counter
the developing resistance to antibiotics, with the
involvement of DZIF’s Clinical Trial Units. Prof
Oliver Cornely, coordinator of the Clinical
Trial Unit of DZIF, becomes the German
The research
coordinator within COMBACTE.
areas, infrastrucThe first
tures and main office
DZIF junior
of DZIF commence
group starts up
operations.
in Bonn under
the direction of
Tanja Schneider.
33
December
November
September
DZIF researchers present their recentlydeveloped potential vaccine against the
newly-emerged coronavirus. It is the first
vaccine candidate publicised worldwide
that could be used as an emergency
vaccine in the event of an epidemic
in humans.
The first
Translational
DZIF- School is held
in Bad Malente.
Virologist and DZIF researcher Prof
Ralf Bartenschlager of Heidelberg
University Hospital receives
the Lautenschläger Research
Prize worth 250,000 euros.
October
First DZIF professor: Marylyn
Addo answers a call to the University Medical Center Hamburg-Eppendorf (UKE), where
she accepts DZIF‘s first W2
professorship. Addo is working
on the early detection and combatting of emerging infectious
diseases.
The representatives of all commonly
established DZIF infrastructures meet for the first time in
Braunschweig to discuss their
capabilities, requirements
and projects.
DZIF Highlights 2013
Prof Mark Brönstrup
accepts a W3 professorship
for Chemical Biology at HZI,
thereby reinforcing DZIF
and its Natural Compound
Library.
34
Science and public
Science and public
Media relations, websites, newsletter:
Getting DZIF talked about
Interface to the public: Janna Schmidt and Karola Neubert reinforce DZIF through communication.
Be it MERS, Ebola, malaria or HIV – infectious diseases and
how to fight them are topics of great public interest. What
are researchers doing against these diseases? How do they
ensure their work reaches the patient? And how are all the
different research disciplines coordinated to make it happen? From the beginning, DZIF has afforded high priority
to maintaining openness and transparency regarding the
aims and methods of its translational research.
Constant communication with the media is essential
The Communications Division commenced work in September 2013. The contacts are Karola Neubert and Janna
Schmidt – two PR officers with long-standing experience
in science and commerce. Their task is to strengthen internal and external communication.
The division has been busy; the essential basis is constant
communication with the media. With more than 200
scientists at locations throughout Germany, the spectrum
of exciting and newsworthy topics is very wide. This can
be seen from an excerpt of press releases from 2013: First
DZIF Professor – Professor Suerbaum is a new member
of Academia Europeae – Award for Ralf Bartenschlager
– Europe concerned: When antibiotics no longer help; “
35
Strong online presence
Just as important as proactive media relations is the upkeep and expansion of the DZIF website. It is continuously
being updated and filled with life. A new category “DZIF
People”, for instance, presents the people behind the
excellent research and the creation of the translational infrastructure. The partner website www.infection-research.
de highlights worldwide trends in research, provides
information on backgrounds and key players, and thereby
positions DZIF as the central contact when it comes to
infection research. In future, DZIF will be concentrating
more strongly on its presence at events and fairs. In the
autumn of 2013, for example, the Helmholtz Centre for
Infection Research organised the series of events “Milestones in Medicine” supported by DZIF. Around 250
interested visitors came to the event to inform themselves
about vaccines, antibiotics and transplants.
Internal communication strengthens social cohesion
Of critical importance for a virtual association such as
DZIF is internal communication. Informing and sharing
are key to successful collaboration. An e-mail newsletter
therefore keeps everyone up to date with news from DZIF.
The first went out at the beginning of 2014.
Science and public
First vaccine against new coronavirus. DZIF has aroused
interest in the media with these and many other topics.
36
Collaboration with scientific institutions and industry
Collaborations
External collaborations
Good collaboration with external partners strengthens DZIF.
Numerous external collaborations at a national
and international level reinforce DZIF’s position as
an outstanding institution in the field of infection
research.
Collaborations with scientific
institutions
University of Freiburg
The epidemiology and diagnostics of tuberculosis are
being researched in a project with the University of Freiburg. One focus is on establishing a diagnostic test (TB
Disc) for detecting resistance and for differentiating clinical isolates in various phylogenetic lines. A lab-on-a-disc
system is being developed for use in field laboratories, for
example at two African partner institutes.
37
German Liver Foundation, Hanover
The HepNet Study House networks trial centres for
hepatitis research and provides a platform for conducting
clinical trials. DZIF can make use of infrastructures and
cohorts for its projects. Current activities are focussing
on hepatitis B, C, D and E. With the German Liver Foundation, a project on hepatic encephalopathy is set to start
in 2014.
Friedrich-Löffler-Institut, Riems
The Friedrich-Löffler-Institut (FLI) is a partner in a collaborative project aimed at the early detection of pathogens transmitted from animals, in particular. This requires
blood and tissue samples and nucleic acid preparations
from domestic and wild animals, as are available at the
FLI.
Hans Knöll Institute, Jena
The Hans Knöll Institute (HKI) is a leading institute in
natural compound research. As an associated partner, it
provides DZIF with natural compounds, in particular from
fungi. One project is testing the pharmacodynamics of
corallopyronin A, a natural product that has already been
successfully tested against filariasis pathogens and is currently undergoing preclinical evaluation. The HKI is largely
responsible for its biosynthesis.
IMI – Innovative Medicines Initiative, Brussels
The Clinical Trial Units of DZIF (DZIF-CTUs) have successfully applied to the Innovative Medicines Initiative –
Joint Undertaking (IMI-JU) of the European Union. Within
the resulting European consortiums (e.g. COMBACTE),
the DZIF-CTUs are involved in trials for combatting
bacterial resistance and will be collaborating with the
industrial partners GlaxoSmithKline, MedImmune and
AstraZeneca.
Infectious Diseases BioBank, London
Since 2013, a cooperation has existed between the DZIF
Biobank and the Infectious Diseases BioBank (IDB) London. The IDB contains, among other things, blood samples
from HIV, hepatitis B and hepatitis C patients, as well as
patients with methicillin-resistant Staphylococcus aureus
infections.
Goethe University Frankfurt am Main
At the Goethe University Frankfurt am Main, a project
focussing on hepatitis is running, in which clinical cohorts
are being established. Blood samples taken from patients
before therapy or after failed therapy are available to all
cooperation partners. The clinical data are being analysed
together with the results of a viral and host gene analysis
and the phenotypic results.
Max Planck Institute for Informatics, Saarbrücken
At the MPI for Informatics in Saarbrücken, data from
hepatitis C patients treated with new antiviral agents
are being gathered as part of a DZIF project (see Goethe
University Frankfurt am Main above) that is intended
to help in making better predictions of the course of the
disease and the response to treatment, and adapting the
treatment individually. By sequencing, analysis and interpretation of the patient and viral genes, along with other
parameters, it should be possible to predict the course of
treatment. In Saarbrücken, the analytical results are being
used to develop an online-based tool.
Robert Koch Institute, Berlin
DZIF is collaborating with the Robert Koch Institute
(RKI) in many fields. Three examples: In the field of
“emerging infections”, the RKI is supporting the strategic
partnership between research institutions, clinics and
pharmaceutical companies. Clinical guidelines are being
developed within of clinical trials. In HIV research, DZIF
can use the new database HIOBs of the RKI.
Collaborations
Charité – Universitätsmedizin Berlin
Charité – Universitätsmedizin Berlin is a partner in a study
on the intelligent use of antibiotics in hospitals. The study
is investigating whether targeted intervention regarding
use of antibiotics in the hospital or practice influences
the frequency of new cases of infections with certain
antibiotic-resistant bacteria. A method for monitoring
multidrug-resistant organisms is being used, which was
developed at Charité with the new module “ATHOS-MRE
Surveillance”.
38
Medical Center – University of Freiburg
In a project with the Medical Center – University of
Freiburg on infections of the immunocompromised host,
scientists are looking to find genetic factors associated
with increased susceptibility to infection. They intend to
find biomarkers that allow better infection control. Focus
is on fungal infections of immunocompromised patients.
Collaborations
A second DZIF project is looking into more targeted use
of antibiotics (see also Charité).
University of Münster
The University of Münster is a partner in a project aimed
at developing new treatment strategies against gastrointestinal infections. In many cases, the antibiotics commonly used nowadays harm the normal gut flora and can lead
to complications. In Münster, the scientists are working on
preventing the complications associated with EHEC.
A second project is working on hospital bugs, and in
particular multidrug-resistant Staphylococcus aureus in the
nasal region. New lytic phage proteins are being studied
for targeted treatment. Their efficiency and specificity will
be analysed in Münster.
Collaborations with industry
Hyglos GmbH, Bernried
The designer-phage proteins currently being developed
against Staphylococcus aureus strains in a DZIF project
(see University of Münster) are being developed and
produced by Hyglos GmbH, Bernried. They are highly
soluble and especially stable – an important prerequisite
for future drug formulations.
Myr GmbH, Burgwedel
Together with the University of Heidelberg, an active
agent (Myrcludex) is being developed that can prevent
hepatitis B viruses from penetrating into cells. Myr GmbH
is coordinating the entire project and overseeing the
clinical trial.
Sanaria Inc., Rockville (USA)
At DZIF Tübingen, scientists are developing a human malaria infection model. The disease is being induced under
controlled conditions in order to test new active agents.
Sanaria Inc. in Rockville, USA, produces malaria parasites
for immunisation purposes, which fulfil all the criteria for
drug approval.
4SC AG, Martinsried
In the TTU “Malaria”, a candidate antimalarial has gone
into preclinical development. SC83288 is being tested as
an inhibitor in the animal model and further developed
in close collaboration with 4SC, which also produces the
active agent.
39
DZG
DZG
German Health Research Centres
The main objective of the German government‘s health
research programme is to develop more effective ways to
combat widespread diseases. The groundwork for this has
been laid at federal and state level with the establishment
of German Health Research Centres as long-term, equal
partnerships between non-university research institutes
and universities with medical centres.
These German Health Research Centres are pooling all of
their existing expertise, thereby greatly helping to close
knowledge gaps and improve prevention, diagnosis and
therapy of the diseases involved. The research policy
ensures close collaboration between basic research
and clinical research, always specifically oriented to the
indications and the patients’ needs. Close networking and
the expansion of existing research structures will allow
faster transfer of research results into clinical practice
(translation).
The strategic cooperation of leading scientists in the
German Health Research Centres promotes Germany to
a high-ranking scientific location and increases its attractiveness to young scientists in Germany and around the
world.
2009 saw the foundation of the “German Centre for Neurodegenerative Diseases” and the “German Centre for
Diabetes Research”. Alongside DZIF, the “German Center
for Cardiovascular Research”, the “German Consortium
for Translational Cancer Research” and the “German Center for Lung Research” were launched in 2012.
From the outset, the six German Health Research Centres
have collaborated closely in order to share their findings
and exploit synergies.
40
Organisation and bodies
Facts and figures
Structure of DZIF
Commission of Funding Authorities
Executive Board
Scientific Advisory Board
The Commission of Funding Authorities –
federal government and respective states
(Länder) – decides on important matters
of finance, organisation and personnel. The
Executive Board and the Managing Director
report to the Commission on all funding
measures.
The Executive Board represents DZIF externally. It implements the resolutions and
tasks assigned by the General Assembly
and is responsible for routine administrative affairs.
The association is supported by a Scientific
Advisory Board of internationally renowned experts from the field of infection
research. The Scientific Advisory Board
advises the Executive Board and General
Assembly on all scientific and programmerelated matters.
Main Office
Internal Advisory Board
The Main Office is located in Braunschweig and supports the Executive Board
in its work. Its duties include organising research initiatives and coordinating DZIF‘s
press and public relations activities.
The members of the Internal Council are
DZIF scientists representing all areas and
locations of the centre. The council
advises the Executive Board on all scientific, programme-related and technical matters and performs representative duties.
Thematic Translational Units (TTU)
Translational Infrastructures (TI)
The Thematic Translational Units bundle the research of the centre.
Each unit dedicates itself to one pathogen or to one specific problem
in infection research.
Strategically aligned translational infection research requires
modern infrastructures. These are provided in the form of the Translational Infrastructures, and can be used by all DZIF members.
Emerging Infections
Tuberculosis
Malaria
HIV
Product Development Unit
Clinical Trial Units
Hepatitis
Gastrointestinal Infections
African Partner Sites
Biobanking
Infections of the immunocompromised Host
Healthcare-associated and
Antibiotic-resistant bacterial
Infections
Natural Compound Library
Bioinformatics
Novel Antiinfectives
DZIF Academy
Partner sites
DZIF conducts its research in 32 research establishments at seven locations throughout Germany. For each site, two scientists are appointed to
coordinate the collaboration and to advise the Main Office. Various external research partners are also involved in DZIF projects.
Bonn-Cologne
Gießen-Marburg-Langen
Hamburg-Lübeck-Borstel
Hannover-Braunschweig
Heidelberg
Munich
Tübingen
Associated Partners
General Assembly
The General Assembly is the central decision-making organ of DZIF. It comprises representatives of the member research establishments of
DZIF. The General Assembly elects the members of the Executive Board and the Executive Director, and decides on the allocation of funds to
the TTUs and TIs.
41
Executive Board
Internal Advisory Board
> Prof Dr M. Krönke, Universität und Universitätsklinikum Köln (Chair)
> Prof Dr U. Protzer, Technische Universität München
und Helmholtz Zentrum München (Vice Chair)
> Prof Dr D. Heinz, Helmholtz-Zentrum für Infektionsforschung, Braunschweig
> Prof Dr I. Autenrieth, Universität und
Universitätsklinikum Tübingen
> Prof Dr K. Cichutek, Paul-Ehrlich-Institut, Langen
> Prof Dr C. Drosten, Universität und
Universitätsklinikum Bonn
> Prof Dr M. Hoelscher, Ludwigs-MaximiliansUniversität München and Klinikum der Universität
München
> Prof Dr R. Horstmann, Bernhard-Nocht-Institut
für Tropenmedizin, Hamburg (Vice Chair)
> Prof Dr H.-G. Kräusslich, Universität und
Universitätsklinikum Heidelberg (Chair)
> Prof Dr T. Schulz, Medizinische Hochschule
Hannover
> Prof Dr T. Welte, Medizinische Hochschule
Hannover
Managing Director
> Dr T. Jäger, DZIF e.V.
Scientific Advisory Board
> Prof Dr P. Alonso, Universitat de Barcelona, Spain
> Prof Dr R. Burger, Robert Koch Institut, Germany
> Prof Dr H. Feldmann, National Institute of Allergy
and Infectious Diseases, USA
> Prof Dr B. B. Finlay, University of British Columbia,
Canada
> Prof Dr A. Friedrich, Universitair Medisch Centrum
Groningen, Netherlands
> Prof Dr B. Kampmann (Chair), Imperial College London,
United Kingdom
> Prof Dr J.-M. Pawlotsky, Université de Paris XII, France
> Prof Dr C. Rooney, Baylor College of Medicine, USA
> Prof Dr H. J. Schmitt, Johannes Gutenberg Universität
Mainz, Germany, and Pfizer Vaccines, France
> Prof Dr A. Telenti, Université de Lausanne, Switzerland
> Prof Dr S. Ward, Liverpool School of Tropical Medicine,
United Kingdom
> Prof Dr R. G. Werner, Universität Tübingen, Germany
Facts and figures
Central bodies
42
Hamburg - Lübeck - Borstel
Hannover - Braunschweig
Bonn - Cologne
Gießen - Marburg - Langen
Heidelberg
Tübingen
Munich
Partner sites and member establishments
43
Germany-wide
infection research
Baden-Württemberg
Tübingen has assumed the coordinating
role in DZIF for Malaria and Healthcareassociated and Antibiotic-resistant
bacterial Infections, and co-coordinators
of Gastrointestinal Infections and Novel
Antiinfectives are working at this location. The main focus in Tübingen is on
the translation of research results into
medicine and vaccine development as
well as on infection models and epidemiology. Regarding infections caused by
antibiotic-resistant, bacterial pathogens,
focus is on improving diagnosis and therapy of multiresistant pathogens such as
methicillin-resistant Staphylococci (MRSA)
and multiresistant gram-negative pathogens (e.g. so-called ESBLs).
Heidelberg
Spokesperson: Prof Dr Hans-Georg
Kräusslich (Heidelberg University)
Establishments: German Cancer Research Center in the Helmholtz Association, Heidelberg University, Heidelberg
University Hospital
TTU coordination:
• Hepatitis (co-coordination)
• HIV (coordination)
• Infections of the Immunocompromised
Host (co-coordination)
• Malaria (co-coordination)
TI coordination:
• Biobanking (coordination)
Tübingen
Spokesperson: Prof Dr Ingo Autenrieth
(University of Tübingen)
Establishments: University of Tübingen,
Max Planck Institute for Developmental
Biology, University Hospital Tübingen
TTU coordination:
• Gastrointestinal Infections (co-coordination)
• Healthcare-associated and Antibioticresistant bacterial Infections (coordination)
• Malaria (coordination)
• Novel Antiinfectives (co-coordination)
Facts and figures
Heidelberg has assumed coordination of
the TTU HIV in DZIF. In order to control
HIV infections, DZIF researchers at this
location are researching factors of the
innate immune system and are identifying sites in the DNA into which the viral
DNA can become integrated. Alongside
HIV, Heidelberg co-coordinates the
TTUs Hepatitis, Malaria and Infections
of the Immunocompromised Host. The
Heidelberg scientists also coordinate the
DZIF-wide translational infrastructure
Biobanking, with focus on establishing
tissue banks.
Facts and figures
44
Bavaria
Hamburg/Schleswig-Holstein
Hessen
The scientists of the Munich DZIF establishments are especially focussed on the
immune control of infections and the development of novel therapies. Pathogenspecific immunotherapies (prophylactic
or therapeutic) aim at strengthening the
body‘s natural defence system so that it
can control specific infectious diseases
more effectively or even avoid them
entirely. Other focuses in Munich are
Gastrointestinal Infections, HIV, Hepatitis
and Tuberculosis.
The Hamburg-Lübeck-Borstel site
combines a unique collection of expertise
and infrastructure for studying infectious diseases and emerging infections
of national and worldwide relevance. It is
involved in clinical, entomological and virological studies. It is the base for medical
chemistry for active agent development
as well as for the epidemiology of malaria
and translational studies on tuberculosis
and hepatitis. The TI African Partner Sites is
coordinated from here.
Munich
Spokesperson: Prof Dr Dirk Busch
(Technische Universität München)
Establishments: Helmholtz Zentrum
München – German Research Center
for Environmental Health, Bundeswehr
Institute of Microbiology, Klinikum der
Universität München, Klinikum rechts
der Isar der Technischen Universität
München, Ludwig-Maximilians-Universität München, Technische Universität
München
TTU coordination:
• Gastrointestinal Infections (co-coordination)
• Hepatitis (co-coordination)
• HIV (co-coordination)
• Infections of the Immunocompromised
Host (coordination)
• Tuberculosis (co-coordination)
TI coordination:
• Biobanking (co-coordination)
• DZIF Academy (coordination)
Hamburg - Lübeck - Borstel
Spokesperson: Prof Dr Rolf Horstmann
(Bernhard Nocht Institute for Tropical
Medicine)
Establishments: Bernhard Nocht Institute for Tropical Medicine in the Leibniz
Association, Research Center Borstel
– Leibniz-Center for Medicine and Biosciences, Heinrich Pette Institute –
Leibniz Institute for Experimental Virology, Universität Hamburg, University
Medical Center Hamburg-Eppendorf,
Universität zu Lübeck
TTU coordination:
• Malaria (co-coordination)
• Emerging Infections (co-coordination)
• Tuberculosis (coordination)
TI coordination:
• African Partner Sites (coordination)
In Gießen-Marburg-Langen, DZIF
researchers are identifying new active
agents and vaccines and producing them
in quality-assured production processes
for scientific and industrial partners.
Research activities are concentrated on
developing strategies for combatting
new or re-emerging infectious diseases
in order to contain outbreaks of new
pathogens for example by quick, effective
action and rapid vaccine development.
Marburg is focusing on viral pathogens,
while Gießen is concentrating on bacteria
and resistance to antibiotics.
Gießen - Marburg - Langen
Spokesperson: Prof Dr Trinad Chakraborty (Giessen University)
Establishments: Gießen University, Paul
Ehrlich Institute Langen, Philipps-Universität Marburg, Mittelhessen University of
Applied Sciences
TTU coordination:
• Healthcare-associated and Antibioticresistant bacterial Infections (co-coordination)
• Emerging Infections (coordination)
TI coordination:
• Bioinformatics (coordination)
• Product Development Unit (coordination)
Lower Saxony
North Rhine-Westphalia
Six Lower Saxon partner institutes
collaborate within DZIF at the Hannover-Braunschweig location. The TTUs
Hepatitis and Gastrointestinal Infections
are coordinated from here. The scientists
here want, among other things, to improve access to hepatitis therapies and are
researching on new diagnostic markers
for the course of infection and therapy.
Also in the researchers’ sights are new
pathogen-specific medicines against pathogens such as EHEC, Helicobacter pylori
or salmonellae. This location is coordinating the establishment of the Natural
Compound Library, which is available to all
DZIF researchers in the search for new
medicines.
Bonn-Cologne coordinates the TTU
Novel Antiinfectives. The DZIF researchers are also researching into faster and
more efficient methods for characterising unknown viral pathogens. Unique in
Germany are the patient cohorts for HIV
and HCV infections as well as HIV/HCV
co-infections. In HIV research, researchers are bringing into translation genetherapy–based strategies for the control
and prophylaxis of these infections. This
location coordinates the DZIF Clinical
Trial Units.
Hannover - Braunschweig
Spokesperson: Prof Dr Sebastian Suerbaum (Hannover Medical School)
Establishments: Helmholtz Centre for
Infection Research, Braunschweig, Leibniz Institute DSMZ – German Collection
of Microorganisms and Cell Cultures,
Hannover Medical School, University of
Veterinary Medicine Hannover, Foundation, Technische Universität Braunschweig,
TWINCORE – Centre for Experimental
and Clinical Infection Research
TTU coordination:
• Gastrointestinal Infections (coordination)
• Hepatitis (coordination)
• Infections of the Immunocompromised
Host (co-coordination)
TI-Koordination:
• Natural Compound Library (coordination)
• Biobanking (co-coordination)
• Bioinformatics (coordination)
Bonn - Köln
Spokesperson: Prof Dr Achim Hörauf
(University of Bonn)
Establishments: University of Bonn,
University Hospital Bonn, University of
Cologne, University Hospital Cologne
TTU coordination:
• Emerging Infections (co-coordination)
• HIV (co-coordination)
• Healthcare-associated and Antibioticresistant bacterial Infections (co-coordination)
• Novel Antiinfectives (coordination)
TI coordination:
• Clinical Trial Units (coordination)
Facts and figures
45
46
Finance
DZIF financial data 2013
2013 expenditure in Euros
By partner sites
3+20+1416127
61+35+4
Gießen-Marburg-Langen
1,031,347
Facts and figures
Heidelberg
1,667,005
Munich
2,065,093
Tübingen
Associated Partners
399,108
2,713,025
Hamburg-Lübeck-Borstel
1,891,451
Bonn-Cologne
1,631,168
By type of expenditure
Hannover-Braunschweig
2,128,865
Investments
582,666
Material Expenses
4,746,653
Personnel
8,197,744
47
Field of work
Emerging Infections
Grants from government and Länder in Euros
Euros
1,242,422
Land
Euros
Baden-Württemberg
329,817
Tuberculosis
527,467
Bavaria
203,549
Malaria
897,476
Hamburg
112,935
HIV
581,677
Hessen
Hepatitis
Gastrointestinal Infections
Infections of the immunocompromised Host
Healthcare-associated and Antibioticresistant bacterial Infections
Novel Antiinfectives
1,181,532
856,952
1,575,547
775,670
1,377,021
Product Development Unit
340,493
Clinical Trial Unit
220,152
African Partner Sites
242,612
Biobanking
553,749
Natural Compound Library
169,439
Bioinformatics
219,216
DZIF Academy
1,161,421
Administration
1,604,218
Total
13,527,063
The expenditure of the German Center for Infection
Research in 2013 was around 13.5 million euros. 98
collaborative projects and 32 stipends were funded within
DZIF in 2013. The majority of funding came from Federal
Government funds (90%) and from Länder funds (10%).
Only departmental research projects of the federal R&D
institutions are fully funded by Germany’s Federal Ministries. Funding Management at the Helmholtz Centre for
Infection Research in Braunschweig forwards the Federal funds to the DZIF partner institutes to support their
projects. Expenditure was reported by the partners in
their interim statements for 2013 and audited by Funding
Management.
75,496
Lower Saxony
271,302
North Rhine-Westphalia
212,887
Schleswig-Holstein
76,210
Financial Contributions from Associated
Partners
38,366
Federal Government
12,206,500
Total
13,527,063
Facts and figures
By field of work
48
Personnel and awards
Employees of DZIF
Full-time equivalent by professional group
1+25+513241715
Professor
0.3
Other
21.5
PhD/MD Student
Facts and figures
23.8
Postdoc
35.9
Total: 142.1
Junior Group Head
7.5
Physician
TA/Study Nurse
34.7
18.4
Full-time equivalent corresponds to a full-time position of the entire fiscal year.
Number of employees by professional group and gender
Professional Groups
Men
Women
Total
Professor
0
1
1
Junior Group Head
15
2
17
Physician
19
18
37
Postdoc
36
51
87
PhD/MD Student
33
52
85
TA/Study Nurse
12
62
74
Other
21
36
57
Total
136
222
358
DZIF recruited 17 employees from abroad and assisted nine mothers on
their return from maternity leave.
49
Laureates
Awards
Prof Dr Ralf Bartenschlager
Heidelberg University Hospital
Lautenschläger Research Prize of Heidelberg University
Yi Chai
Helmholtz Centre for Infection Research
Chinese Government Award 2013 For Outstanding Self-Financed
Students Abroad of the China Scholarship Council
PD Dr Sandra Ciesek
Hannover Medical School
2013 Yael Prize of the German Association for the Study of the Liver
(GASL)
Prof Dr Petra Dersch
Helmholtz Centre for Infection Research
2013 Main Prize of the German Society for Hygiene and Microbiology (DGHM)
Dr Jan Felix Drexler
University of Bonn
Heine-Medin Award of the European Society for Clinical Virology
PD Dr Thomas von Hahn
Hannover Medical School
2013 Rising Stars Award of United European Gastroenterology
Prof Dr Gunther Hartmann
University of Bonn
Selection into the German National Academy of Sciences Leopoldina
Thomas Hoffmann
Helmholtz Centre for Infection Research
2013 Poster Prize at the 25th European Conference on Natural
Products of DECHEMA
Liujie Huo
Helmholtz Centre for Infection Research
2013 Young Scientist Meeting Grant of the Federation of European
Microbiological Societies
Liujie Huo
Helmholtz Centre for Infection Research
Chinese Government Award 2013 For Outstanding Self-Financed
Students Abroad of the China Scholarship Council
Prof Dr Helge Karch
University of Münster
2013 Robert Koch Prize for Hospital Hygiene and Infection
Prevention
Prof Dr Helge Karch
University of Münster
2013 Research Award of the University of Münster
Dr Benno Kreuels
University Medical Center Hamburg-Eppendorf
Award for second-best lecture of the German Tropical Medicine
Society (DGT)
Prof Dr Dr h.c. Christoph Lange
Research Center Borstel
Awarded honorary doctorate by Moldova State University, Chisinau,
Moldova
Prof Dr Sebastian Suerbaum
Hannover Medical School
Selection into the European Academy of Sciences Academia
Europaea
Facts and figures
Awards and commendations
50
Publications
Scientific achievements 2013
1. Abass E, Bollig N, Reinhard K, Camara B,
Mansour D, Visekruna A, Lohoff M, Steinhoff
U (2013) rKLO8, a Novel Leishmania donovani –
Derived Recombinant Immunodominant Protein
for Sensitive Detection of Visceral Leishmaniasis in
Sudan. PLOS Negl Trop Dis, 7(7):e2322
Publications
2. Aburizaiza AS, Mattes FM, Azhar EI, Hassan
AM, Memish ZA, Muth D, Meyer B, Lattwein
E, Müller MA, Drosten C (2014) Investigation of
anti-middle East respiratory syndrome antibodies in
blood donors and slaughterhouse workers in Jeddah
and Makkah, Saudi Arabia, fall 2012. J Infect Dis,
209(2):243-6 (Epub 2013)
10. Andreu N, Zelmer A, Sampson S L, Ikeh M,
Bancroft GJ, Schaible UE, Wiles S, Robertson BD
(2013) Rapid in vivo assessment of drug efficacy against
Mycobacterium tuberculosis using an improved firefly
luciferase. J Antimicrob Chemother, 68(9):2118-27
11. Angenvoort J, Brault AC, Bowen RA, Groschup
MH (2013) West Nile viral infection of equids. Vet
Microbiol, 167(1-2):168-80
12. Bartenschlager R, Lohmann V, Penin F (2013)
The molecular and structural basis of advanced antiviral
therapy for hepatitis C virus infection. Nat Rev Microbiol, 11(7):482-496
3. Adlhoch C, Kaiser M, Kingsley MT, Schwarz
NG, Ulrich M, de Paula VS, Ehlers J, Löwa A,
Daniel AM, Poppert S, Schmidt-Chanasit J, Ellerbrok H (2013) Porcine hokovirus in domestic pigs,
Cameroon. Emerg Infect Dis, 19(12):2060-2962
13. Beck J, Echtenacher B, Ebel F (2013) Woronin
bodies, their impact on stress resistance and virulence
of the pathogenic mould Aspergillus fumigatus and their
anchoring at the septal pore of filamentous Ascomycota.
Mol Microbiol, 89(5):857-71
4. Al Rushood M, McCusker C, Mazer B,
Alizadehfar R, Grimbacher B, Depner M, BenShoshan M (2013) Autosomal Dominant Cases
of Chronic Mucocutaneous Candidiasis Segregates
with Mutations of Signal Transducer and Activator
of Transcription 1, But Not of Toll-Like Receptor 3. J
Pediatr, 163(1):277-9
14. Becker N, Geier M, Balczun C, Bradersen U,
Huber K, Kiel E, Krüger A, Lühken R, Orendt C,
Plenge-Böning A, Rose A, Schaub GA, Tannich E
(2013) Repeated introduction of Aedes albopictus
into Germany, July to October 2012. Parasitol Res,
112(4):1787-1790
5. Alduina R, Gallo G, Renzone G, Weber T,
Scaloni A, Puglia AM (2014) Novel Amycolatopsis balhimycina biochemical abilities unveiled by
proteomics. FEMS Microbiol Lett, 351:209-15
(Epub 2013)
6. Aleksic E, Merker M, Cox H, Reiher B, Sekawi
Z, Hearps AC, Ryan CE, Lee AV, Goursaud R,
Malau C, O‘Connor J, Cherry CL, Niemann S,
Crowe SM (2013) First molecular epidemiology
study of Mycobacterium tuberculosis in Kiribati.
PLOS ONE, 8(1):e55423
7. Allix-Béguec C, Wahl C, Hanekom M, Nikolayevskyy V, Drobniewski F, Maeda S, CamposHerrero I, Mokrousov I, Niemann S, Kontsevaya I,
Rastogi N, Samper S, Sng LH, Warren RM, Supply
P (2013) Proposal of a consensus set of hypervariable mycobacterial interspersed repetitive-unitvariable-number tandem-repeat loci for subtyping of
Mycobacterium tuberculosis Beijing isolates. J Clin
Microbiol, 52(1):164-72
8. Allweiss L, Volz T, Lütgehetmann M, Giersch
K, Bornscheuer T, Lohse AW, Petersen J, Ma H,
Klumpp K, Fletcher SP, Dandri M (2014) Immune
cell responses are not required to induce substantial
hepatitis B virus antigen decline during pegylated interferon-alpha administration. J Hepatol,
60(3):500-7 (Epub 2013)
9. Ameres S, Mautner J, Schlott F, Neuenhahn M,
Busch DH, Plachter B, Moosmann A (2013) Presentation of an immunodominant immediate-early
CD8+ T cell epitope resists human cytomegalovirus
immunoevasion. PLOS Pathogens, 9(5):e1003383
15. Beggel B, Neumann-Fraune M, Kaiser R,
Verheyen J, Lengauer T (2013) Inferring short-range
linkage information from sequencing chromatograms.
PLOS ONE, 8(12):e81687
16. Bierbaum G, Sahl HG (2014) The search for new
anti-infective drugs: untapped resources and strategies.
Int J Med Microbiol, 304(1):1-2 (Epub 2013 Oct 11)
21. Borchers S, Ogonek J, Varanasi P, Tischer S,
Bremm M, Eiz-Vesper B, Koehl U, Weissinger
EM (2014) Multimer monitoring of CMV-specific T
cells in research and in clinical applications. (Review)
Diagn Microbiol Infect Dis, 78(3):201-212 (Epub
2013)
22. Borchers S, Weissinger EM, Pabst B, Ganzenmueller T, Dammann E, Luther S, Diedrich H,
Ganser A, Stadler M (2013) Expansion of recipientderived antiviral T cells may influence donor
chimerism after allogeneic stem cell transplantation.
Transpl Infect Dis, 15(6):627-33
23. Borst EM, Kleine-Albers J, Gabaev I, Babic
M, Wagner K, Binz A, Degenhardt I, Kalesse M,
Jonjic S, Bauerfeind R, Messerle M (2013) The
human cytomegalovirus UL51 protein is essential for
viral genome cleavage-packaging and interacts with
the terminase subunits pUL56 and pUL89. J Virol,
87(3):1720-32
24. Borst EM, Ständker L, Wagner K, Schulz TF,
Forssmann WG, Messerle M (2013) A peptide
inhibitor of cytomegalovirus infection from human
hemofiltrate. Antimicrob Agents Chemother,
57(10):4751-60
25. Bryant JM, Harris SR, Parkhill J, Dawson R,
Diacon AH, van Helden P, Pym A, Mahayiddin AA,
Chuchottaworn C, Sanne IM, Louw C, Boeree
MJ, Hoelscher M, McHugh TD, Bateson AL,
Hunt RD, Mwaigwisya S, Wright L, Gillespie SH,
Bentley SD (2013) Whole-genome sequencing to
establish relapse or re-infection with Mycobacterium
tuberculosis: a retrospective observational study.
Lancet Respir Med, 1(10):786-792
17. Bindt C, Guo N, Bonle MT, Appiah-Poku J, Hinz R,
Barthel D, Schoppen S, Feldt T, Barkmann C, Koffi M,
Loag W, Nguah SB, Eberhardt KA, Tagbor H, N‘goran
E, Ehrhardt S (2013) International CDS Study Group.
No association between antenatal common mental
disorders in low-obstretic risk woman and adverse birth
outcomes in their offspring: results from the CDS study in
Ghana and Cote D’Ivoire. PLOS ONE, 8:e80711
26. Buchholz U, Müller MA, Nitsche A, Sanewski
A, Wevering N, Bauer-Balci T, Bonin F, Drosten
C, Schweiger B, Wolff T, Muth D, Meyer B, Buda
S, Krause G, Schaade L, Haas W (2013) Contact
investigation of a case of human novel coronavirus
infection treated in a German hospital, OctoberNovember 2012. Euro Surveill, 18(8)
18. Blin K, Medema MH, Kazempour D, Fischbach MA, Breitling R, Takano E, Weber T (2013)
antiSMASH 2.0 – a versatile platform for genome mining
of secondary metabolite producers. Nucl Acids Res,
41,W204-W212
27. Buchholz VR, Flossdorf M, Hensel I, Kretschmer L, Weissbrich B, Gräf P, Verschoor A, Schiemann M, Höfer T, Busch DH (2013) Disparate individual fates compose robust CD8+ T cell immunity.
Science, 340(6132):630-5
19. Bogner JR, Kutaiman A, Esguerra-Alcalen M,
Heldner S, Arvis P (2013) Moxifloxacin in complicated
skin and skin structure infections (cSSSIs): A prospective,
international, non-interventional, observational study.
Adv Ther, 30(6):630-43
28. Buchholz VR, Gräf P, Busch DH (2013) The
smallest unit: effector and memory CD8+ T cell differentiation on the single cell level. Front Immunol,
4:31
20. Bonsor DA, Weiss E, Iosub-Amir A, Reingewertz
TH, Chen TW, Haas R, Friedler A, Fischer W, Sundberg EJ (2013) Characterization of the Translocationcompetent Complex between the Helicobacter pylori
Oncogenic Protein CagA and the Accessory Protein
CagF. J Biol Chem, 288(46):32897-32909
29. Bunse CE, Borchers S, Varanasi PR, Tischer
S, Figueiredo C, Immenschuh S, Kalinke U, Koehl
U, Goudeva L, Maecker-Kolhoff B, Ganser A,
Blasczyk R, Maecker-Kolhoff B, Weissinger EM,
Eiz-Vesper B (2013) Impaired functionality of
antiviral T cells in G-CSF mobilized stem cell donors:
Implications for the selection of CTL donor. PLOS
ONE, 8(12):e77925
51
31. Chegou NN, Heyckendorf J, Walzl G, Lange
C, Ruhwald M (2014) Beyond the IFN-γ horizon:
Biomarkers for immunodiagnosis of infection with M.
tuberculosis. Eur Respir J, 43(5):1472-86 (Epub
2013)
32. Ching W, Koyuncu E, Singh S, Arbelo-Roman
C, Hartl B, Kremmer E, Speiseder T, Meier C,
Dobner T (2013) A Ubiquitin-specific Protease
Possesses a Decisive Role for Adenovirus Replication
and Oncogene-mediated Transformation. PLOS
Pathogens, 9(3):e1003273, 1-18
33. Comas I, Coscolla M, Luo T, Borrell S, Holt
KE, Kato-Maeda M, Parkhill J, Malla B, Berg S,
Thwaites G, Yeboah-Manu D, Bothamley G, Mei
J, Wei L, Bentley S, Harris SR, Niemann S, Diel
R, Aseffa A, Gao Q, Young D, Gagneux S (2013)
Out-of-Africa migration and Neolithic coexpansion of
Mycobacterium tuberculosis with modern humans.
Nat Genet, 45(10):1176-82
34. Corman VM, Eickmann M, Landt O, Bleicker
T, Brünink S, Eschbach-Bludau M, Matrosovich
M, Becker S, Drosten C (2013) Specific detection
by real-time reverse-transcription PCR assays of a
novel avian influenza A(H7N9) strain associated with
human spillover infections in China. Euro Surveill,
18(16):20461
35. Corman VM, Kallies R, Philipps H, Göpner
G, Müller MA, Eckerle I, Brünink S, Drosten C,
Drexler JF (2014) Characterization of a novel
betacoronavirus related to middle East respiratory
syndrome coronavirus in European hedgehogs.
J Virol, 88(1):717-24 (Epub 2013)
36. Dammermann W, Schipper P, Ullrich S, Fraedrich K, Schulze Zur Wiesch J, Fründt T, Tiegs
G, Lohse A, Lüth S (2013) Increased expression of
complement regulators CD55 and CD59 on peripheral blood cells in patients with EAHEC O104:H4
infection. PLOS ONE, 8(9):e74880
37. de Groot RJ, Baker SC, Baric RS, Brown CS,
Drosten C, Enjuanes L, Fouchier RA, Galiano M,
Gorbalenya AE, Memish ZA, Perlman S, Poon
LL, Snijder EJ, Stephens GM, Woo PC, Zaki
AM, Zambon M, Ziebuhr J (2013) Middle East
respiratory syndrome coronavirus (MERS-CoV):
announcement of the Coronavirus Study Group.
J Virol, 87(14):7790-92
38. de Paula VS, Wiele M, Mbunkah AH, Daniel
AM, Kingsley MT, Schmidt-Chanasit J (2013)
Hepatitis E virus genotype 3 strains in domestic pigs,
Cameroon. Emerg Infect Dis, 19(4):666-668
39. Deest M, Westhaus S, Steinmann E, Manns MP,
von Hahn T, Ciesek S (2014) Impact of single nucleotide polymorphisms in the essential HCV entry factor
CD81 on HCV infectivity and neutralization. Antiviral
Res, 101:37-44 (Epub 2013)
40. Diel R, Loddenkemper R, Zellweger JP, Sotgiu
G, D‘Ambrosio L, Centis R, van der Werf MJ, Dara
M, Detjen A, Gondrie P, Reichman L, Blasi F, Migliori
GB; European Forum for TB Innovation (2013)
Old ideas to innovate tuberculosis control: preventive treatment to achieve elimination. Eur Respir J,
42(3):785-801
41. Dill T, Dobler G, Saathoff E, Clowes P, Kroidl
I, Ntinginya E, Machibya H, Maboko L, Löscher T,
Hoelscher M, Heinrich N (2013) High Seroprevalence for Typhus Group Rickettsiae in Mbeya Region,
Southwestern Tanzania, is associated with Sparse
Vegetation and Proximity to a Highway. Emerg Infect
Dis, 19(2):317-20
42. Dössinger G, Bunse M, Bet J, Albrecht J, Paszkiewicz PJ, Weißbrich B, Schiedewitz I, Henkel L,
Schiemann M, Neuenhahn M, Uckert W, Busch DH
(2013) MHC multimer-guided and cell culture-independent isolation of functional T cell receptors from
single cells facilitates TCR identification for immunotherapy. PLOS ONE, 8(4):e61384
43. Drexler JF, Corman VM, Müller MA, Lukashev
AN, Gmyl A, Coutard B, Adam A, Ritz D, Leijten LM,
van Riel D, Kallies R, Klose SM, Gloza-Rausch F, Binger T, Annan A, Adu-Sarkodie Y, Oppong S, Bourgarel M, Rupp D, Hoffmann B, Schlegel M, Kümmerer
BM, Krüger DH, Schmidt-Chanasit J, Setién AA,
Cottontail VM, Hemachudha T, Wacharapluesadee
S, Osterrieder K, Bartenschlager R, Matthee S,
Beer M, Kuiken T, Reusken C, Leroy EM, Ulrich RG,
Drosten C (2013) Evidence for novel hepaciviruses in
rodents. PLOS Pathog, 9(6):e1003438
44. Drexler JF, Geipel A, König A, Corman VM,
van Riel D, Leijten LM, Bremer CM, Rasche A,
Cottontail VM, Maganga GD, Schlegel M, Müller
MA, Adam A, Klose SM, Carneiro AJ, Stöcker A,
Franke CR, Gloza-Rausch F, Geyer J, Annan A, AduSarkodie Y, Oppong S, Binger T, Vallo P, Tschapka M,
Ulrich RG, Gerlich WH, Leroy E, Kuiken T, Glebe D,
Drosten C (2013) Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus and
capable of infecting human hepatocytes. Proc Natl
Acad Sci USA, 110(40):16151-6
45. Drosten C (2013) Is MERS another SARS? Lancet
Infect Dis, 13(9):727-8
46. Drosten C, Seilmaier M, Corman VM, Hartmann
W, Scheible G, Sack S, Guggemos W, Kallies R, Muth
D, Junglen S, Müller MA, Haas W, Guberina H, Röhnisch T, Schmid-Wendtner M, Aldabbagh S, Dittmer
U, Gold H, Graf P, Bonin F, Rambaut A, Wendtner
CM (2013) Clinical features and virological analysis of
a case of Middle East respiratory syndrome coronavirus
infection. Lancet Infect Dis, 13(9):745-51
47. Ehren K, Hertenstein C, Kümmerle T, Vehreschild JJ, Fischer J, Gillor D, Wyen C, Lehmann
C, Cornely OA, Jung N, Gravemann S, Platten
M, Wasmuth JC, Rockstroh JK, Boesecke C,
Schwarze-Zander C, Fätkenheuer G (2014)
Causes of death in HIV-infected patients from the
Cologne-Bonn cohort. Infection, 42(1):135-40
(Epub 2013)
48. Elgaher WAM, Fruth M, Groh M, Haupenthal
J, Hartmann RW (2014) Expanding the scaffold
for bacterial RNA polymerase inhibitors: design,
synthesis and structure–activity relationships of ureidoheterocyclic- carboxylic acids. RSC Advances,
4,2177-2194
49. Esser-Nobis K, Romero-Brey I, Ganten TM,
Gouttenoire J, Harak C, Klein R, Schemmer P,
Binder M, Schnitzler P, Moradpour D, Bartenschlager R, Polyak SJ, Stremmel W, Penin F,
Eisenbach C, Lohmann V (2013) Analysis of hepatitis C virus resistance to silibinin in vitro and in vivo
points to a novel mechanism involving nonstructural
protein 4B. Hepatology, 57(3):953-963
50. Felder S, Dreisigacker S, Kehraus S, Neu E,
Bierbaum G, Wright PR, Menche D, Schäberle
TF, König GM (2013) Salimabromide: Unexpected
Chemistry from the Obligate Marine Myxobacterium
Enhygromyxa salina. Chemistry – A European
Journal, 19(28):9319-9324
51. Felder S, Kehraus S, Neu E, Bierbaum G, Schäberle TF, König GM (2013) Salimyxins and Enhygrolides: Antibiotic, Sponge-Related Metabolites from
the Obligate Marine Myxobacterium Enhygromyxa
salina. ChemBioChem, 14(11):1363-1371
52. Feuerriegel S, Köser CU, Richter E, Niemann
S (2013) Mycobacterium canettii is intrinsically
resistant to both pyrazinamide and pyrazinoic acid. J
Antimicrob Chemother, 68(6):1439-40
53. Fomsgaard A, Fertner ME, Essbauer S, Nielsen AY, Frey S, Lindblom P, Lindgren PE, Bødker
R, Weidmann M, Dobler G (2013) Tick-borne
encephalitis virus, Zealand, Denmark, 2011. Emerg
Infect Dis, 19(7):1171-3
54. Formichella L, Romberg L, Bolz C, Vieth M,
Geppert M, Göttner G, Nölting C, Walter D,
Schepp W, Schneider A, Ulm K, Wolf P, Busch
DH, Soutschek E, Gerhard M(2013) A Novel Line
Immunoassay Based on Recombinant Virulence
Factors Enables Highly Specific and Sensitive Serologic Diagnosis of Helicobacter pylori Infection. Clin
Vaccine Immunol, 20(11):1703-1710
55. Frangoulidis D, Splettstoesser WD, Landt O,
Dehnhardt J, Henning K, Hilbert A, Bauer T, Antwerpen M, Meyer H, Walter MC, Knobloch JK
(2013) Microevolution of the chromosomal region of
acute disease antigen A (adaA) in the query (Q) fever
agent Coxiella burnettii. PLOS ONE, 8(1):e53440
Publications
30. Cebula M, Ochel A, Hillebrand Z, Pils MC,
Schirmbeck R, Hauser H, Wirth D (2013) An
inducible transgenic mouse model for immune
mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells. PLOS ONE,
8(7):e68720
Publications
52
56. Frey S, Essbauer S, Zöller G, Klempa B,
Weidmann M, Dobler G, Pfeffer M (2013) Complete Genome Sequence of Tick-Borne Encephalitis
Virus Strain A104 Isolated from a Yellow-Necked
Mouse (Apodemus flavicollis) in Austria. Genome
Announcements, 1(4):e00564-13
64. Garigliany MM, Marlier D, Tenner-Racz K,
Eiden M, Cassart D, Gandar F, Beer M, SchmidtChanasit J, Desmecht D (2014) Detection of Usutu
virus in a bull- finch (Pyrrhula pyrrhula) and a great
spotted woodpecker (Dendrocopos major) in northwest Europe. Vet J, 199(1):191-3 (Epub 2013)
73. Gustems M, Woellmer A, Rothbauer U, Eck
SH, Wieland T, Lutter D, Hammerschmidt W
(2014) c-Jun/c-Fos heterodimers regulate cellular
genes via a newly identified class of methylated DNA
sequence motifs. Nucleic Acids Res, 42(5):30593072 (Epub 2013)
57. Frickmann H, Dekker D, Boahen K, Acquah
S, Sarpong N, Adu-Sarkodie Y, Schwarz NG, May
J, Marks F, Poppert S, Wiemer DF, Hagen RM
(2013) Increased detection of invasive enteropathogenic bacteria in pre-incubated blood culture materials by real-time PCR in comparison with automated
incubation in Sub-Saharan Africa. Scand J Infect
Dis, 45(8):616-22
65. Giersch K, Helbig M, Volz T, Allweiss L,
Mancke LV, Lohse AW, Polywka S, Pollok JM,
Petersen J, Taylor J, Dandri M, Lütgehetmann M
(2014) Persistent hepatitis D virus mono-infection in
humanized mice is efficiently converted by hepatitis
B virus to a productive co-infection. J Hepatol,
60(3):538-44 (Epub 2013)
74. Guo N, Bindt C, Te Bonle M, Appiah-Poku J,
Hinz R, Barthel D, Koffi M, Posdzich S, Deymann
S, Barkmann C, Schlüter L, Jaeger A, Blay Nguah
S, Eberhardt KA, N‘goran E, Tagbor H, Ehrhardt S
for the International CDS Study Group (2013) Association of antepartum and postpartum depression
in Ghanaian and Ivorian women with febrile illness in
their offspring: A prospective birth cohort study. Am
J Epidemiol, 178(9):1394-402
58. Frickmann H, Hänle A, Essig A, Dekker D,
Boahen K, Acquah S, Sarpong N, Adu-Sarkodie Y,
Schwarz NG, May J, Marks F, Hagen RM, Poppert
S (2013) Fluorescence in situ hybridization (FISH) for
rapid identification of Salmonella spp. from agar and
blood culture broth--an option for the tropics? Int J
Med Microbiol, 303(5):277-84
59. Frickmann H, Schwarz NG, Girmann M,
Hagen RM, Poppert S, Crusius S, Podbielski A,
Heriniaina JN, Razafindrabe T, Rakotondrainiarivelo JP, May J, Rakotozandrindrainy R (2013)
Serological survey on HIV and Syphilis in pregnant
women in Madagascar. Trop Med Int Health,
18(1):35-9
60. Frickmann H*, Schwarz NG*, Holtherm HU,
Maassen W, Vorderwulbecke F, Erkens K, Fischer
M, Morwinsky T, Hagen RM, *contributed equally
(2013) Compliance with antimalarial chemoprophylaxis in German soldiers: a 6-year survey. Infection,
41(2):311-320
61. Frickmann H, Tenner-Racz K, Eggert P,
Schwarz NG, Poppert S, Tannich E, Hagen RM
(2013) Influence of parasite density and sample storage time on the reliability of Entamoeba
histolytica-specific PCR from formalin-fixed and
paraffin-embedded tissues. Diagn Mol Pathol,
22(4):236-244
62. Friedrich SO, Rachow A, Saathoff E, Singh
K, Mangu CD, Dawson R, Phillips PP, Venter A,
Bateson A, Boehme CC, Heinrich N, Hunt RD,
Boeree MJ, Zumla A, McHugh TD, Gillespie SH,
Diacon AH, Hoelscher M (2013) Assessment of the
sensitivity and specificity of Xpert MTB/RIF assay as
an early sputum biomarker of response to tuberculosis treatment.Lancet Respir Med, 1(6):462-470
63. Gabriel M, Emmerich P, Frank C, Fiedler
M, Rashidi-Alavijeh J, Jochum C, Günther S,
Auerhammer K, Rupprecht HJ, Blank RT, Sacher
N, Pertzborn L, Stark K, Schrauzer T, SchmidtChanasit J (2013) Increase in West Nile virus
infections imported to Germany in 2012. J Clin
Virol, 58(3):587-589
66. Glässner A, Eisenhardt M, Kokordelis P,
Krämer B, Wolter F, Nischalke HD, Boesecke C,
Sauerbruch T, Rockstroh JK, Spengler U, Nattermann J (2013) Impaired CD4* T cell stimulation
of NK cell anti-fibrotic activity may contribute to
accelerated liver fibrosis progression in HIV/HCV
patients. J Hepatol, 59(3):427-33
67. Glebe D, Bremer (2013) The Molecular
Virology of Hepatitis B Virus. Semin Liver Dis,
33(2):103-12
68. Greil J, Rausch T, Giese T, Bandapalli OR,
Daniel V, Bekeredjian-Ding I, Stutz AM, Drees C,
Roth S, Ruland J, Korbel JO, Kulozik AE (2013)
Whole-exome sequencing links caspase recruitment
domain 11 (CARD11) inactivation to severe combined immunodeficiency. J Allergy Clin Immunol,
131(5):1376-1383
69. Gronbach K, Flade I, Holst O, Lindner B,
Ruscheweyh HJ, Wittmann A, Menz S, Schwiertz
A, Adam P, Stecher B, Josenhans C, Suerbaum
S, Gruber AD, Kulik A, Huson D, Autenrieth IB,
Frick JS (2014) Endotoxicity of lipopolysaccharide
as a determinant of T-cell-mediated colitis induction
in mice. Gastroenterology, 146(3):765-775 (Epub
2013)
70. Gruber I, Heudorf U, Werner G, Pfeifer Y,
Imirzalioglu C, Ackermann H, Brandt C, Besier
S, Wichelhaus TA (2013) Multidrug-resistant
bacteria in geriatric clinics, nursing homes, and ambulant care-prevalence and risk factors. Int J Med
Microbiol, 303(8):405-9
71. Guenther S, Wuttke J, Bethe A, Vojtech
J, Schaufler K, Semmler T, Ulrich RG, Wieler
LH, Ewers C (2013) Is fecal carriage of extendedspectrum-β-lactamase-pro-ducing Escherichia coli
in urban rats a risk for public health? Antimicrob
Agents Chemother, 57(5):2424-2425
72. Gupta M, Miller CJ, Baker JV, Lazar J, Bogner
JR, Calmy A, Soliman EZ, Neaton JD; INSIGHT
SMART Study Group (2013) Biomarkers and electrocardiographic evidence of myocardial ischemia
in patients with human immunodeficiency virus
infection. Am J Cardiol, 111(5):760-4
75. Haas CS, Lehne W, Muck P, Boehm A, Rupp J,
Steinhoff J, Lehnert H (2013) Acute kidney injury
and thrombocytopenic fever – consider the infrequent causes. Am J Emerg Med, 31(2):441.e5-9
76. Hagen RM, Wulff B, Loderstaedt U, Fengler
I, Frickmann H, Schwarz NG, Polywka S (2013) Is
rapid hepatitis C virus testing from corpses a screening option for index persons who have died after
mass-casualty incidents in high-prevalence settings
in the field? J R Army Med Corps, doi:10.1136/
jramc-2013-000133
77. Hammamy MZ, Haase C, Hammami M, Hilgenfeld R, Steinmetzer T (2013) Development and
characterization of new peptidomimetic inhibitors of
the West Nile virus NS2B-NS3. Chem Med Chem,
8(2):231-41
78. Hantz S, Cotin S, Borst E, Couvreux A,
Salmier A, Garrigue I, Merville P, Mengelle C,
Attal M, Messerle M, Alain S (2013) Novel DNA
polymerase mutations conferring cytomegalovirus
resistance: input of BAC-recombinant phenotyping
and 3D model. Antiviral Res, 98(1):130-4
79. Hauck D, Joachim I, Frommeyer B, Varrot
A, Philipp B, Möller HM, Imberty A, Exner TE,
Titz A (2013) Discovery of Two Classes of Potent
Glycomimetic Inhibitors of Pseudomonas aeruginosa
LecB with Distinct Binding Modes. ACS Chem Biol,
8(8):1775–1784
80. Hauswaldt S, Nitschke M, Sayk F, Solbach
W, Knobloch JK (2013) Lessons Learned from
Outbreaks of Shiga Toxin Producing Escherichia coli.
Curr Infect Dis Rep, 15(1):4-9
81. Heimann SM, Cornely OA, Vehreschild MJ,
Glossmann J, Kochanek M, Kreuzer KA, Hallek
M, Vehreschild JJ (2014) Treatment cost development of patients undergoing remission induction
chemotherapy: a pharma coeconomic analysis before
and after introduction of posaconazole prophylaxis.
Mycoses, 57(2):90-7 (Epub 2013)
53
91. Jabara HH, Ohsumi T, Chou J, Massaad MJ,
Benson H, Megarbane A, Chouery E, Mikhael
R, Gorka O, Gewies A, Portales P, Nakayama T,
Hosokawa H, Revy P, Herrod H, Le Deist F, Lefranc
G, Ruland J, Geha RS (2013) A homozygous mucosaassociated lymphoid tissue 1 (MALT1) mutation in a
family with combined immunodeficiency. J Allergy
Clin Immunol, 132(1):151-158
83. Hilgenfeld R, Peiris M (2013) From SARS to
MERS: 10 years of research on highly pathogenic human coronaviruses. Antiviral Res, 100(1):286-295
92. Jafari C, Ernst M, Kalsdorf B, Lange C (2013)
Comparison of molecular and immunological methods
for the rapid diagnosis of smear-negative tuberculosis.
Int J Tuberc Lung Dis, 17(11):1459-65
84. Hitkova I, Yuan G, Anderl F, Gerhard M,
Kirchner T, Reu S, Röcken C, Schäfer C, Schmid
RM, Vogelmann R, Ebert MP, Burgermeister E
(2013) Caveolin-1 protects B6129 mice against
Helicobacter pylori gastritis. PLOS Pathogens,
9(4):e1003251
85. Hoffmann J, Boehm C, Himmelsbach K, Donnerhak C, Roettger H, Weiss TS, Ploen D, Hildt
E (2013) Identification of α-taxilin as an essential
factor for the life cycle of hepatitis B virus. J Hepatol,
59(5):934-41
86. Hoffmann C, Kohrs F, Sabranski M, Wolf E,
Jaeger H, Wyen C, Siehl J, Baumgarten A, Hensel
M, Jessen A, Schaaf B, Vogel M, Bogner J, Horst
HA, Stephan C (2013) HIV-associated lung cancer:
survival in an unselected cohort. Scand J Infect Dis,
45(10):766-72
87. Hoffmann D, Mauroy A, Seebach J, Simon
V, Wantia N, Protzer U (2013) New norovirus
classified as a recombinant GII.g/GII.1 causes an
extended foodborne outbreak at a university hospital
in Munich. J Clin Virol, 58(1):24-30
88. Huang LR, Wohlleber D, Reisinger F, Jenne
CN, Cheng RL, Abdullah Z, Schildberg FA,
Odenthal M, Dienes HP, van Rooijen N, Schmitt
E, Garbi N, Croft M, Kurts C, Kubes P, Protzer U,
Heikenwalder M, Knolle PA (2013) Intrahepatic
myeloid-cell aggregates enable local proliferation
of CD8(+) T cells and successful immunotherapy
against chronic viral liver infection. Nat Immunol,
14(6):574-583
89. Horwitz JA, Halper-Stromberg A, Mouquet
H, Gitlin AD, Tretiakova A, Eisenreich TR, Malbec
M, Gravemann S, Billerbeck E, Dorner M, Büning
H, Schwartz O, Knops E, Kaiser R, Seaman MS,
Wilson JM, Rice CM, Ploss A, Bjorkman PJ, Klein
F, Nussenzweig MC (2013) HIV-1 suppression and
durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized
mice. Proc Natl Acad Sci USA, 110(41):16538-43
90. Huebner J, Rack-Hoch AL, Pecar A, Schmid
I, Klein C, Borde JP (2013) Pilot project of a
pediatric antibiotic stewardship initiative at the
Hauner children‘s hospital. Klinische Pädiatrie,
225(4):223-9
101. Kayigire XA, Friedrich SO, Venter A, Dawson
R, Gillespie SH, Boeree MJ, Heinrich N, Hoelscher
M, Diacon AH (2013) Direct comparison of Xpert
MTB/RIF with liquid and solid mycobacterial culture for
the quantification of early bactericidal activity. J Clin
Microbiol, 51(6):1894-8
102. Kirchner T, Hermann E, Möller S, Klinger M,
Solbach W, Laskay T, Behnen M (2013) Flavonoides
and 5-aminosalicylic acid inhibit the formation of
neutrophil extracellular traps. Mediators Inflamm,
2013:710239
93. Jiménez-Soto LF, Clausen S, Sprenger A, Ertl C,
Haas R (2013) Dynamics of the Cag-type IV secretion
system of Helicobacter pylori as studied by bacterial
co-infections. Cellular Microbiol, 15(11):19241937
103. Koehler RN, Alter G, Tovanabutra S, Saathoff E,
Arroyo MA, Walsh AM, Sanders-Buell EE, Maboko L,
Hoelscher M, Robb ML, Michael NL, McCutchan FE,
Kim JH, Kijak GH (2013) Natural killer cell-mediated
innate sieve effect on HIV-1: the impact of KIR/HLA
polymorphism on HIV-1 subtype-specific acquisition in
East Africa. J Infect Dis, 208(8):1250-4
94. Josten M, Reif M, Szekat C, Al-Sabti N, Roemer
T, Sparbier K, Kostrzewa M, Rohde H, Sahl HG,
Bierbaum G (2013) Analysis of the matrix-assisted
laser desorption ionization-time of flight mass spectrum of Staphylococcus aureus identifies mutations that
allow differentiation of the main clonal lineages. J Clin
Microbiol, 51(6):1809-17
104. Kopp A, Gillespie TR, Hobelsberger D, Estrada
A, Harper JM, Miller RA, Eckerle I, Müller MA,
Podsiadlowski L, Leendertz FH, Drosten C, Junglen
S (2013) Provenance and geographic spread of St. Louis
encephalitis virus. Mbio, 4(3):e00322-13
95. Junglen S, Drosten C (2013) Virus discovery and
recent insights into virus diversity in arthropods. Curr
Opin Microbiol, 16(4):507-513
105. Koryakina I, McArthur J, Randall S, Draelos
MM, Musiol EM, Muddiman DC, Weber T, Williams
GJ (2013) Poly specific trans-acyltransferase machinery
revealed via engineered acyl-CoA synthetases. ACS
Chem Biol, 8(1):200-8
96. Kaebisch R, Mejías-Luque R, Prinz C, Gerhard
M (2014) Helicobacter pylori cytotoxin-associated
gene A impairs human dendritic cell maturation and
function through IL-10-mediated activation of STAT3.
J Immunol, 192(1):316-323 (epub 2013)
97. Kalsdorf B, Skolimowska KH, Scriba TJ, Dawson
R, Dheda K, Wood K, Hofmeister J, Hanekom WA,
Lange C, Wilkinson RJ (2013) Relationship between
chemokine receptor expression, chemokine levels
and HIV-1 replication in the lungs of persons exposed
to Mycobacterium tuberculosis. Eur J Immunol,
43(2):540-549
106. Krämer B, Nischalke HD, Boesecke C, Ingiliz P,
Voigt E, Mauss S, Stellbrink HJ, Baumgarten A, Rockstroh JK, Spengler U, Nattermann J (2013) Variation
in IFNL4 genotype and response to interferon-based
therapy of hepatitis C in HIV-positive patients with acute
and chronic hepatitis C. AIDS, 27(17):2817-2819
107. Krebes J, Morgan RD, Bunk B, Spröer C, Luong
K, Parusel R, Anton BP, König C, Josenhans C, Overmann J, Roberts RJ, Korlach J, Suerbaum S (2014)
The complex methylome of the human gastric pathogen
Helicobacter pylori. Nucleic Acids Res, 42(4):24152432 (Epub 2013)
98. Kang H*, Kreuels B*, Adjei O, Krumkamp R, May
J, Small DS. *equally contributed (2013) The causal
effect of malaria on stunting: a Mendelian randomization and matching approach. Int J Epidemiol,
42:1390-1398
108. Krüger A, Tannich E (2013) Rediscovery of
Anopheles algeriensis Theob. (Diptera: Culicidae) in
Germany after half a century. Eur Mosq Bulletin,
31:14-16
99. Kast K, Berens-Riha N, Zeynudin A, Abduselam
N, Eshetu T, Löscher T, Andreas Wieser A, Shock
J, Pritsch M (2013) Evaluation of Plasmodium falciparum gametocyte detection in different patient material.
Malar J, 12:438
109. Krumkamp R, Sarpong N, Kreuels B, Ehlkes L,
Loag W, Schwarz N, Zeeb H, Adu-Sarkodie Y, May
J (2013) Health care utilization and symptom severity
in Ghanaian children – a cross-sectional study. PLOS
ONE, 8(11):e80598
100. Kawai K, Meydani SN, Urassa W, Wu D, Mugusi FM, Saathoff E, Bosch RJ, Villamor E, Spiegelman
D, Fawzi WW (2014) Micronutrient supplementation
and T cell-mediated immune responses in patients
with tuberculosis in Tanzania. Epidemiol Infect,
142(7):1505-9 (Epub 2013)
110. Kuenne C, Billion A, Mraheil MA, Strittmatter A,
Daniel R, Goesmann A, Barbuddhe S, Hain T, Chakraborty T (2013) Reassessment of the Listeria monocytogenes pan-genome reveals dynamic integration hotspots
and mobile genetic elements as major components of the
accessory genome. BMC Genomics, 14:47:00
Publications
82. Hellberg, L, Samavedam UK, Holdorf K, Hänsel
M, Recke A, Beckmann T, Steinhorst K, Boehncke
WH, Kirchner T, Möckel N, Solbach W, Zillikens D,
Schmidt E, Ludwig RJ, Laskay T (2013) Methylprednisolone blocks autoantibody-induced tissue damage in
experimental models of bullous pemphigoid and epidermolysis bullosa acquisita through inhibition of neutrophil activation. J Invest Dermatol, 133(10):2390-9
54
111. Kurokawa K, Jung DJ, Ana JH, Fuchs K, Jeon
YJ, Kim NH, Li X, Tateishi K, Park JA, Xia G, Matsushita M, Takahashi K, Park HJ, Peschel A, Lee BL
(2013) Glycoepitopes of staphylococcal wall teichoic
acid govern complement-mediated opsonophagocytosis via human serum antibody and mannose-binding
letin. J Biol Chem, 288(43):30956-68
Publications
112. Kutscher S, Dembek CJ, Deckert S, Russo
C, Körber N, Bogner JR, Geisler F, Umgelter A,
Neuenhahn M, Albrecht J, Cosma A, Protzer U,
Bauer T (2013) Overnight Resting of PBMC Changes
Functional Signatures of Antigen Specific T- Cell Responses: Impact for Immune Monitoring within Clinical
Trials. PLOS ONE, 8(10):e76215
113. Lanternier F, Pathan S, Vincent QB, Liu L,
Cypowyj S, Prando C, Migaud M, Taibi L, AmmarKhodja A, Boudghene Stambouli O, Guellil B,
Jacobs F, Goffard JC, Schepers K, del Marmol V,
Boussofara L, Denguezli M, Larif M, Bachelez H,
Michel L, Lefranc G, Hay R, Jouvion G, Chretien F,
Fraitag S, Bougnoux ME, Boudia M, Abel L, Lortholary O, Casanova JL*, Picard C*, Grimbacher B*, Puel
A*. *contributed equally and are considered aequo
loco (2013) Deep dermatophytosis and inherited
CARD9 deficiency. N Engl J Med, 369(18):1704-14
114. Lentz CS, Stumpfe D, Bajorat J, Famulok M,
Hoerauf A, Pfarr KM (2013) New chemotypes for
wALADin1-like inhibitorsof delta-aminolevulinic acid
dehydratase from Wolbachia endobacteria. Bioorg
MedChemLett, 23(20): 5558-5562
115. Leung CC, Lange C, Zhang Y (2013) Tuberculosis: current state of knowledge: an epilogue. Respirology, 18(7):1047-55
116. Liang F, Bond E, Sandgren KJ, Smed-Sörensen
A, Rangaka MX, Lange C, Koup RA, McComsey GA,
Lederman MM, Wilkinson RJ, Andersson J, Loré K
(2013) Dendritic cell recruitment in response to skin
antigen tests in HIV-1-infected individuals correlates
with the level of T-cell infiltration. AIDS.
117. Lu I, Eberhard J, Ahmad F, Bhatnagar N,
Behrens G, Jacobs R, Schmidt RE, Meyer-Olson
D (2014) Elevated CD57 and CD95 expressions
are associated with lower numbers of CD4⁺ recent
thymic emigrants in HIV-1 infected immune responders
following antiretroviral treatment. Immunol Lett,
158(1-2):1-6 (Epub 2013)
118. Lupberger J, Schaedler S, Peiran A, Hildt E
(2013) Identification and characterization of a novel
bipartite nuclear localization signal in the hepatitis B virus polymerase. World J Gastroenterol,
19(44):8000-10
119. Lutz P, Parcina M, Bekeredjian-Ding I, Hoerauf
A, Strassburg CP, Spengler U (2014) Spontaneous
bacterial peritonitis by Pasteurella multocida under
treatment with rifaximin. Infection, 42(1):175-7
(Epub 2013)
120. Mann PA, Müller A, Xiao L, Pereira PM,
Yang C, Lee SH, Wang H, Trzeciak J, Schneeweis J, Dos Santos MM, Murgolo N, She X,
Gill C, Balibar CJ, Labroli M, Su J, Flattery A,
Sherborne B, Maier R, Tan CM, Black T, Onder
K, Kargman S, Monsma FJ, Pinho MG, Schneider
T, Roemer T (2013) Murgocil is a Highly Bioactive
Staphylococcal-specific Inhibitor of the Peptidoglycan Glycosyltransferase Enzyme MurG. ACS Chem
Biol, 8(11):2442-51
121. Marklewitz M, Zirkel F, Rwego IB,
Heidemann H, Trippner P, Kurth A, Kallies R,
Briese T, Lipkin WI, Drosten C, Gillespie TR,
Junglen S (2013) Discovery of a unique novel
clade of mosquito-associated bunyaviruses. J Virol,
87(23):12850-65
122. Mast Y, Wohlleben W (2014) Streptogramins - Two are better than one! Int J Med Microbiol, 304:44-50 (Epub 2013)
123. Merker M, Kohl TA, Roetzer A, Truebe L,
Richter E, Rüsch-Gerdes S, Fattorini L, Oggioni
MR, Cox H, Varaine F, Niemann S (2013) Whole
genome sequencing reveals complex evolution
patterns of multidrug-resistant Mycobacterium
tuberculosis Beijing strains in patients. PLOS ONE,
8(12):e82551
124. Mshana SE, Hain T, Domann E, Lyamuya EF,
Chakraborty T, Imirzalioglu C (2013) Predominance of Klebsiella pneumoniae ST14 carrying
CTX-M-15 causing neonatal sepsis in Tanzania.
BMC Infect Dis, 13:466
125. Mullen L, Rigby A, Sclanders M, Adams G,
Mittal G, Colston J, Fatah R, Subang C, Foster J,
Francis-West P, Koster M, Hauser H, Layward
L, Vessillier S, Annenkov A, Al-Izki S, Pryce G,
Bolton C, Baker D, Gould D J, Chernajovsky Y
(2013) Latency can be conferred to a variety of
cytokines by fusion with latency-associated peptide
from TGF-beta. Expert Opin Drug Deliv, 11(1):516 (Epub 2013)
126. Müller-Berghaus J, Volkers P, Scherer J, Cichutek K (2013) Besonderheit bei der Regulierung
biologischer Arzneimittel in der individualisierten
Medizin. Bundesgesundheitsbl – Gesundheitsforsch – Gesundheitsschutz , 56:1538-1544
127. Müller C, Dietz I, Tziotis D, Moritz F, Rupp
J, Schmitt-Kopplin P (2013) Molecular cartography in acute Chlamydia pneumoniae infections
– a non-targeted metabolomics approach. Anal
Bioanal Chem, 405(15):5119-31
128. Mueller MC, Walentiny C, Seybold U,
Nöstlinger C, Platteau T, Borms R, Draenert
R, Bogner JR (2013) Sexual and reproductive
health services for people living with HIV/AIDS in
Germany: are we up to the challenge? Infection,
41:761-768
129. Musiol EM, Greule A, Härtner T, Wohlleben
W, Weber T (2013) The AT2 Domain of KirCI Loads
Malonyl Extender Units to the ACPs of the Kirromycin
PKS. ChemBioChem, 14(11):1343-52
130. Nandakumar R, Nair S, Neumann B, Finsterbusch K, Grashoff M, Hochnadel I, Lienenklaus S,
Wappler I, Steinmann E, Hauser H, Pietschmann
T, Kröger A (2013) Hepatitis C Virus replication
in mouse cells is restricted by IFN-dependent and
IFN-independent mechanisms. Gastroenterology,
145(6):1414-23.e1
131. Nauerth M, Weissbrich B, Busch DH (2013)
The clinical potential for koff-rate measurement
in adoptive immunotherapy. Expert Reviews,
9(12):1151-3
132. Nauerth M, Weißbrich B, Knall R, Franz T,
Dössinger G, Bet J, Paszkiewicz PJ, Pfeifer L, Bunse
M, Uckert W, Holtappels R, Gillert-Marien D, Neuenhahn M, Krackhardt A, Reddehase MJ, Riddell
SR, Busch DH (2013) TCR-ligand koff rate correlates
with the protective capacity of antigen-specific CD8+
T cells for adoptive transfer. Science Translational
Medicine, 5(192):192ra87
133. Neuenhahn M, Busch DH (2013) Whole-body
anatomy of human T cells. Immunity, 38(1):10-2
134. Nkongolo S, Ni Y, Lempp FA, Kaufman C, Lindner T, Esser-Nobis K, Lohmann V, Mier W, Mehrle
S, Urban S (2014) Cyclosporin A inhibits hepatitis B
and hepatitis D virus entry by cyclophilin-independent
interference with the NTCP receptor. J Hepatol,
60(4):723-731 (Epub 2013)
135. Overmann, J (2013) Principles of enrichment,
isolation, cultivation, and preservation of bacteria. The
Prokaryotes, 4th edition, Prokaryotic Biology and
Symbiotic Associations. Springer, New York, pp
149-207
136. Pan KF, Formichella L, Zhang L, Zhang Y, Ma
JL, Li ZX, Liu C, Wang YM, Goettner G, Ulm K, Classen M, You WC, Gerhard M (2013) Helicobacter pylori antibody responses and evolution of precancerous
gastric lesions in a Chinese population. International
Journal of Cancer, 134(9):2118-25
137. Pavlova S, Feederle R, Gärtner K, Fuchs W,
Granzow H, Delecluse HJ (2013) An Epstein-Barr
virus mutant produces immunogenic defective particles
devoid of viral DNA. J Virol, 87(4):2011-22
138. Phillips PP, Bratton DJ, Nunn AJ, Hoelscher
M (2013) Reply to Dodd and Proschan. J Infect Dis,
207(3):544-5
139. Ploen D, Hafirassou ML, Himmelsbach K,
Schille SA, Biniossek ML, Baumert TF, Schuster C,
Hildt E (2013) TIP47 is associated with the hepatitis
C virus and its interaction with Rab9 is required for release of viral particles. Eur J Cell Biol, 92(12):374-82
55
141. Rau SJ, Hildt E, Himmelsbach K, Thimme R,
Wakita T, Blum HE, Fischer R (2013) CD40 inhibits
replication of hepatitis C virus in primary human
hepatocytes by c-Jun N terminal kinase activation
independent from the interferon pathway. Hepatology,
57(1):23-36
142. Reiling N, Homolka S, Walter K, Brandenburg
J, Niwinski L, Ernst M, Herzmann C, Lange C, Diel R,
Ehlers S, Niemann S (2013) Clade-specific virulence
patterns of Mycobacterium tuberculosis complex strains
in human primary macrophages and aerogenically
infected mice. MBio, 4(4):e00250-13
143. Reusken CB, Haagmans BL, Müller MA,
Gutierrez C, Godeke GJ, Meyer B, Muth D, Raj VS,
Smits-De Vries L, Corman VM, Drexler JF, Smits SL,
El Tahir YE, De Sousa R, van Beek J, Nowotny N, van
Maanen K, Hidalgo-Hermoso E, Bosch BJ, Rottier P,
Osterhaus A, Gortázar-Schmidt C, Drosten C, Koopmans MP (2013) Middle East respiratory syndrome
coronavirus neutralising serum antibodies in dromedary
camels: a comparative serological study. Lancet Infect
Dis, 13(10):859-66
144. Rieger T, Merkler D, Günther S (2013) Infection
of Type I Interferon Receptor-Deficient Mice with
Various Old World Arenaviruses: A Model for Studying
Virulence and Host Species Barriers. PLOS ONE,
8(8):e72290
145. Riess H, Clowes P, Kroidl I, Kowuor DO, Nsojo
A, Mangu C, Schüle SA, Mansmann U, Geldmacher
C, Mhina S, Maboko L, Hoelscher M, Saathoff E
(2013) Hookworm infection and environmental factors
in mbeya region, Tanzania: a cross-sectional, populationbased study. PLOS Negl Trop Dis, 7(9):e2408
146. Roemer T, Schneider T, Pinho MG (2013)
Accessory Factors: A chink in the Armor of MRSA Resistance to β-lactam Antibiotics. Curr Opin Microbiol,
16(5):538-48
147. Roetzer A, Diel R, Kohl TA, Rückert C, Nübel
U, Blom J, Wirth T, Jaenicke S, Schuback S, RüschGerdes S, Supply P, Kalinowski J, Niemann S (2013)
Whole genome sequencing versus traditional genotyping for investigation of a Mycobacterium tuberculosis
outbreak: a longitudinal molecular epidemiological
study. PLOS Med, 10(2):e1001387
148. Roider J, Kalteis AL, Vollbrecht T, Gloning L,
Stirner R, Henrich N, Bogner JR, Draenert R (2013)
Adaptation of CD8 T cell responses to changing HIV-1
sequences in a cohort of HIV-1 infected individuals
not selected for a certain HLA allele. PLOS ONE,
8(12):e80045
149. Rojas-Ponce G, Rachow A, Guerra H,
Mapamba D, Joseph J, Mlundi R, Marimoto S,
Ntinginya NE, Mangu C, Framhein A, Butler
A, Kohlenberg A, Ngatemelela D, Froeschl G,
Maboko L, Hoelscher M, Heinrich N (2013) A
continuously monitored colorimetric method for
detection of Mycobacterium tuberculosis complex in
sputum. Int J Tuberc Lung Dis, 17(12):1607-12
150. Rolling T, Wichmann D, Schmiedel S, Burchard GD, Kluge S, Cramer JP (2013) Artesunate
versus quinine in the treatment of severe imported
malaria: comparative analysis of adverse events
focussing on delayed haemolysis. Malar J, 12:241
151. Rotta Detto Loria J, Rohmann K, Droemann D, Kujath P, Rupp J, Goldmann T, Dalhoff
K (2013) Nontypeable Haemophilus Influenzae
Infection Upregulates the NLRP3 Inflammasome
and Leads to Caspase-1-Dependent Secretion of
Interleukin-1ß-A Possible Pathway of Exacerbations
in COPD. PLOS ONE, 8(6):e66818
152. Rubbenstroth D, Ryll M, Knobloch JK,
Köhler B, Rautenschlein S (2013) Evaluation of
different diagnostic tools for the detection and identification of Riemerella anatipestifer. Avian Pathol,
42(1):17-26
153. Rückert C, Szczepanowski R, Albersmeier
A, Goesmann A, Iftime D, Musiol EM, Blin K,
Wohlleben W, Pühler A, Kalinowski J, Weber T
(2013) Complete genome sequence of the kirromycin producer Streptomyces collinus Tü 365 consisting
of a linear chromosome and two linear plasmids. J
Biotechnol, 168:739-40
154. Rudolf M, Czajka C, Börstler J, Melaun C,
Jöst H, von Thien H, Badusche M, Becker N,
Schmidt-Chanasit J, Krüger A, Tannich E, Becker
S (2013) First nationwide surveillance of Culex
pipiens complex and Culex torrentium mosquitoes
demonstrated the presence of Culex pipiens biotype
pipiens / molestus hybrids in Germany. PLOS ONE,
8(9):e71832
158. Schmid H, Tokarska-Schlattner M, Füeßl B,
Röder M, Kay L, Attia S, Lederer SR, Goebel FD,
Schlattner U, Bogner JR (2013) Macro CK2 accumulation in tenofovir-treated HIV patients is facilitated by CK oligomer stabilization but is not predictive
for pathology. Antivir Therapy, 18(2):193-204
159. Schmidt SK, Ebel S, Keil E, Woite C, Ernst
JF, Benzin AE, Rupp J, Däubener W (2013) Regulation of IDO activity by oxygen supply: inhibitory
effects on antimicrobial and immunoregulatory
functions. PLOS ONE, 8(5):e63301
160. Schmitt C, Raggub L, Linnenweber-Held S,
Adams O, Schwarz A, Heim A (2014) Donor origin
of BKV replication after kidney transplantation. J
Clin Virol, 59(2):120-125 (Epub 2013)
161. Schneider T, Müller A, Miess H, Gross H
(2014) Cyclic lipopeptides as antibacterial agents
- potent antibiotic activity mediated by intriguing
mode of actions. Int J Med Microbiol, 304(1):3743 (Epub 2013)
162. Schommers P, Wyen C, Hentrich M, Gillor
D, Zoufaly A, Jensen B, Bogner JR, Thoden
J, Wasmuth JC, Fätkenheuer G, Hoffmann C
(2013) Poor outcome of HIV-infected patients with
plasmablastic lymphoma: results from the German
AIDS-related lymphoma cohort study. AIDS,
27(5):842-5
163. Schorn M, Zettler J, Noel JP, Dorrestein P,
Moore BS, Kaysser L (2014) The genetic basis for
the biosynthesis of the pharmaceutically important
class of epoxyketone proteasome inhibitors. ACS
Chemical Biology, 9(1):301-309 (Epub 2013)
164. Schweikart J, May J (2013) Malaria – nur ein
Problem der Tropen? Hyg Med, 38[9]: 366-371
165. Sethi S, Nanda R, Chakraborty T (2013)
Clinical application of volatile organic compound
analysis for detecting infectious diseases. Clin
Microbiol Rev, 26(3):462-475
155. Sahner JH, Groh M, Negri M, Haupenthal J,
Hartmann RW (2013) Novel small molecule inhibitors targeting the “switch region” of bacterial RNAP:
Structure-based optimization of a virtual screening
hit. Eur J Med Chem, 65,223-231
166. Shima K, Klinger M, Solbach W, Rupp J
(2013) Activities of first-choice antimicrobials
against gamma interferin-treated Chlamydia
trachomatis differ in hypnoxia. Antimicrob Agents
Chemother, 57(6):2828-30
156. Schäberle TF, Schiefer A, Schmitz A, König
GM, Hoerauf A, Pfarr K (2014) Corallopyronin A –
A promising antibiotic for treatment of filariasis. Int J
Med Microbiol, 304(1):72-78 (Epub 2013)
167. Söhngen C, Bunk B, Podstawka A, Gleim D,
Overmann J (2014) BacDive – The Bacterial Diversity Metadatabase. Nucl Acids Res, 42:D592D599 (Epub 2013)
157. Schiefer A, Vollmer J, Lämmer C, Specht S,
Lenty C, Ruebsamen-Schaeff H, Brötz-Osterhelt
H, Hoerauf A, Pfarr K (2013) The Wolbachia ClpP
protease is a novel endobacterial target for antifilarial therapy. J Antimicrob Chemother, 68 (8):
1790-1800
168. Sola-Landa A, Rodríguez-García A, Amin
R, Wohlleben W, Martín JF (2013) Competition
between the GlnR and PhoP regulators for the glnA
and amtB promoters in Streptomyces coelicolor.
Nucleic Acids Res, 41:1767-82
Publications
140. Raj VS, Mou H, Smits SL, Dekkers DH, Müller
MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus
AD, Bosch BJ, Haagmans BL (2013) Dipeptidyl peptidase 4 is a functional receptor for the emerging human
coronavirus-EMC. Nature, 495(7440):251-4
56
169. Song F, Fux R, Provacia LB, Volz A, Eickmann
M, Becker S, Osterhaus AD, Haagmans BL,
Sutter G (2013) Middle East respiratory syndrome
coronavirus spike protein delivered by modified
vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. J Virol, 87(21):11950-4
180. Tessema B, Beer J, Merker M, Emmrich F,
Sack U, Rodloff AC, Niemann S (2013) Molecular
epidemiology and transmission dynamics of Mycobacterium tuberculosis in Northwest Ethiopia: new
phylogenetic lineages found in Northwest Ethiopia.
BMC Infect Dis, 13:131
170. Specht S, Debrah AY, Klarmann U, Mand S,
Hoerauf A, Pfarr K (2013) Chemotherapy of filariasis - established strategies and new developments.
GMS Infect Dis, 1:1-10
181. Theilacker C, Held J, Allering L, Emmerich P,
Schmidt-Chanasit J, Kern WV, Panning M (2013)
Prolonged polyarthralgia in a German traveller with
Mayaro virus infection without inflammatory correlates. BMC Infect Dis, 13(1):369
Publications
171. Spinner CD, Noe S, Schwerdtfeger C, Todorova A, Gaa J, Schmid RM, Busch DH, Neuenhahn M (2013) Acute hypophysitis and hypopituitarism in early syphilitic meningitis in a HIV-infected
patient: a case report. BMC Infect Dis, 13:481
172. Sprinzl MF, Russo C, Kittner J, Allgayer S,
Grambihler A, Bartsch B, Weinmann A, Galle
PR, Schuchmann M, Protzer U, Bauer T (2013)
Hepatitis B virus-specific T-cell responses during IFN
administration in a small cohort of chronic hepatitis
B patients under nucleos(t)ide analogue treatment. J
Viral Hepatitis, doi: 10.1111/jvh.12189
173. Stauga S, Hahn A, Brattig NW, Fischer-Herr
J, Baldus S, Burchard GD, Cramer JP (2013) Clinical relevance of different biomarkers in imported
plasmodium falciparum malaria in adults: a case
control study. Malar J, 12:246
174. Stecher B (2013) Finding a sugary foothold:
how antibiotics pave the way for enteric pathogens.
Cell Host Microbe, 14(3):225-227
175. Stecher B, Maier L, Hardt WD (2013)
‘Blooming‘ in the gut: how dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol,
11(4):277-284
176. Sucipto H, Wenzel SC, Müller R (2013)
Exploring chemical diversity of α-pyrone antibiotics:
molecular basis of myxopyronin biosynthesis.
ChemBioChem, 14(13):1581-1589
177. Suerbaum S (2013) The bugs within: interdisciplinary approaches to studying host-associated
microbiota. FEMS Rev Microbiol, 37:633
178. Szaszak M, Shima K, Käding N, Hannus
M, Solbach W, Rupp J (2013) Host metabolism
promotes growth of Chlamydia pneumoniae ina
low oxygen environment. Int J Med Microbiol,
303(5):239-46
179. Tan J, George S, Kusov Y, Perbandt M,
Anemüller S, Mesters JR, Norder H, Coutard
B, Lacroix C, Leyssen P, Neyts J, Hilgenfeld R
(2013) 3C protease of enterovirus 68: Structurebased design of Michael acceptor inhibitors and
their broad-spectrum antiviral effects against
picornaviruses. J Virol, 87(8):4339-4351
182. Theron G, Zijenah L, Chanda D, Clowes P,
Rachow A, Lesosky M, Bara W, Mungofa S, Pai M,
Hoelscher M, Dowdy D, Pym A, Mwaba P, Mason
P, Peter J, Dheda K; TB-NEAT team (2014) Feasibility, accuracy, and clinical effect of point-of-care
Xpert MTB/RIF testing for tuberculosis in primarycare settings in Africa: a multicentre, randomised,
controlled trial. Lancet, 383(9915):424-435
(Epub 2013)
183. Thoden J, Potthoff A, Bogner JR, Brockmeyer NH, Esser S, Grabmeier-Pfistershammer
K, Haas B, Hahn K, Härter G, Hartmann M, Herzmann C, Hutterer J, Jordan AR, Lange C, Mauss
S, Meyer-Olson D, Mosthaf F, Oette M, Reuter
S, Rieger A, Rosenkranz T, Ruhnke M, Schaaf B,
Schwarze S, Stellbrink HJ, Stocker H, Stoehr A,
Stoll M, Träder C, Vogel M, Wagner D, Wyen C,
Hoffmann C (2013) Therapy and prophylaxis of
opportunistic infections in HIV-infected patients: a
guideline by the German and Austrian AIDS societies
(DAIG/ÖAG) (AWMF 055/066). Infection, 41
Suppl 2:S91-115
184. Tóth I, Le AQ, Hartjen P, Thomssen A,
Matzat V, Lehmann C, Scheurich C, Beisel C,
Busch P, Degen O, Lohse AW, Eiermann T,
Fätkenheuer G, Meyer-Olson D, Bockhorn M,
Hauber J, van Lunzen J, Schulze Zur Wiesch J
(2013) Decreased frequency of CD73+CD8+ T cells
of HIV-infected patients correlates with immune
activation and T cell exhaustion. J Leukoc Biol,
94(4):551-61
185. Towhid ST, Schmidt EM, Tolios A, Münzer P,
Schmidt E, Borst O, Gawaz M, Stegmann O, Lang
F (2013) Stimulation of platelet death by vancomycin. Cell Physiol Biochem, 31:102-12
186. Towhid ST, Tolios A, Münzer P, Schmidt EM,
Borst O, Gawaz M, Stegmann E, Lang F (2013)
Stimulation of platelet apoptosis by balhimycin.
Biochem Biophys Res Commun, 435:323-6
187. Tschan S, Brouwer AJ, Werkhoven PR,
Jonker AM, Wagner L, Knittel S, Aminake MN,
Pradel G, Joanny F, Liskamp RM, Mordmüller
B (2013) Broad-spectrum antimalarial activity of
peptido sulfonyl fluorides, a new class of proteasome inhibitors. Antimicrob Agents Chemother,
57(8):3576-3584
188. Vehreschild JJ (2013) Pneumonia and Lung
Infiltrates in Neutropenic Patients: Many Stones
Unturned. Ann Am Thorac Soc, 10(5):493-5
189. Vehreschild JJ, Morgen G, Cornely OA,
Hartmann P, Koch S, Kalka-Moll W, Wyen C,
Vehreschild MJ, Lehmann C, Gillor D, Seifert
H, Kremer G, Fätkenheuer G, Jung N (2013)
Evaluation of an infectious disease consultation programme in a German tertiary care hospital. Infection,
41(6):1121-8
190. Vehreschild M, Cornely OA (2013) Intestinal
colonisation and blood stream infections due to vancomycin-resistant enterococci (VRE) and extendedspectrum beta-lactamase-producing Enterobacteriaceae (ESBLE) in patients with haematological and
oncological malignancies. Infection, 41(5):1049-50
191. Vereide DT, Seto E, Chiu YF, Hayes M, Tagawa T, Grundhoff A, Hammerschmidt W, Sugden B
(2013) Epstein-Barr virus maintains lymphomas via
its miRNAs. Oncogene, 33(10):1258-1264 (Epub
2013)
192. Vollmer J, Schiefer A, Schneider T, Jülicher K,
Johnston KL, Taylor MJ, Sahl HG, Hoerauf A, Pfarr
K (2013) Requirement of lipid II biosynthesis for cell
division in cell wall-less Wolbachia, endobacteria of
arthropods and filarial nematodes. Int J Med Microbiol, 303: 140-149
193. Volz T, Allweiss L, M Barek MB, Warlich M,
Lohse AW, Pollok JM, Alexandrov A, Urban S,
Petersen J, Lütgehetmann M, Dandri M (2013)
The entry inhibitor Myrcludex-B efficiently blocks
intrahepatic virus spreading in humanized mice
previously infected with hepatitis B virus. J Hepatol,
58:861-7
194. Vonberg RP, Höhle M, Aepfelbacher M, Bange FC, Belmar Campos C, Claussen K, Christner
M, Cramer JP, Haller H, Hornef M, Fickenscher
H, Fraedrich K, Knobloch JK, Kühbacher T,
Manns MP, Nitschke M,Peter G, Pulz M, Rohde H,
Roseland RT, Sayk F, Schaumburg F, Schöcklmann
HO, Schubert S, Solbach W, Karch H, Suerbaum
S (2013) Duraction of fecal shedding of Shiga
toxisn-producing Escherichia coli o104:H4 in patients
infected during the 2011 outbreak in Germany: a
multicenter study. Clin Infect Dis, 56(8):1132-40
195. Wang R, Mast Y, Wang J, Zhang W, Zhao G,
Wohlleben W, Lu Y, Jiang W (2013) Identification
of two-component system AfsQ1/Q2 regulon and its
cross-regulation with GlnR in Streptomyces coelicolor.
Mol Microbiol, 87(1):30-48
196. Weidmann M, Frey S, Freire C, Essbauer S,
Ruzek D, Klempa B, Zubrikova D, Vögerl M, Pfeffer M, Hufert FT, Zanotto PM, Dobler G (2013)
Molecular phylogeography of tick-borne encephalitis virus in central Europe. J General Virology,
94:2129-2139
57
198. Wiegand J, Wedemeyer H, Franke A, Rößler S,
Zeuzem S, Teuber G, Wächtler M, Römmele U, Ruf
B, Spengler U, Trautwein C, Bock CT, Fiedler GM,
Thiery J, Manns MP, Brosteanu O, Tillmann HL, the
German Hep-Net Acute Hepatitis B (GAHB) Study
Group (2013) Treatment of severe, nonfulminant
acute hepatitis B with lamivudine vs placebo: a prospective randomized double-blinded multicentre trial. J
Viral Hepatitis, doi: 10.1111/jvh.12210
199. Wilmes M, Sahl HG (2014) Defensin-based
anti-infective strategies. Int J Med Microbiol,
304(1):93-9 (Epub 2013 Sep 4)
200. Winstel V, Liang C, Sanchez-Carballo P, Steglic
M, Munar M, Bröker BM, Penadés JR, Nübel U,
Holst O, Dandekar T, Peschel A, Xia G (2013)
Wall teichoic acid structure governs horizontal gene
transfer between major bacterial pathogens. Nat
Commun, 4:2345 8038
201. Winstel V, Xia G, Peschel A (2014) Pathways
and roles of wall teichoic acid glycosylation in
Staphylococcus aureus. Int J Med Microbiol, 304(34):215-21(Epub 2013)
202. Xia G, Wolz C (2014) Phages of Staphylococcus
aureus and their impact on host evolution. Infect
Genet Evol, 21:593-601 (Epub 2013)
203. Yang I, Nell S, Suerbaum S (2013) Surviving
in hostile territory: The microbiota of the stomach.
IFEMS Rev Microbiol, 37:736-761
204. Yang I, Eibach D, Kops F, Brenneke B,
Woltemate S, Schulze J, Bleich A, Gruber AD,
Muthupalani S, Fox JG, Josenhans C, Suerbaum S
(2013) Intestinal microbiota composition of interleukin-10 deficient C57BL/6J mice and susceptibility to
Helicobacter hepaticus-induced colitis. PLOS ONE,
8:e70783
205. Ye F, Zhang J, Liu H, Hilgenfeld R, Zhang R,
Kong X, Li L, Lu J, Zhang X, Li D, Jiang H, Yang CG,
Luo C (2013) Helix unfolding/refolding characterizes
the functional dynamics of Staphylococcus aureus Clp
protease. J Biol Chem, 288(24):17643-53
206. Zhou P, Chen Z, Yan Q, Yang S, Hilgenfeld R,
Jiang Z (2013) The structure of a glycoside hydrolase
family 81 endo-ß-1,3-glicanase. Acta Crystallogr D
Biol Crystallogr, 69(Pt 10):2027-38
207. Ziegler U, Angenvoort J, Klaus C, Nagel-Kohl
U, Sauerwald C, Thalheim S, Horner S, Braun
B, Kenklies S, Tyczka J, Keller M, Groschup MH
(2013) Use of competition ELISA for monitoring of
West Nile virus infections in horses in Germany. Int J
Environ Res Public Health, 10(8):3112-20
208. Zielecki F, Weber M, Eickmann M, Spiegelberg L, Zaki AM, Matrosovich M, Becker S,
Weber F (2013) Human cell tropism and innate
immune system interactions of human respiratory
coronavirus EMC compared to those of severe
acute respiratory syndrome coronavirus. J Virol,
87(9):5300-4
209. Zirkel F, Roth H, Kurth A, Drosten C,
Ziebuhr J, Junglen S (2013) Identification and
characterization of genetically divergent members of
the newly established family Mesoniviridae. J Virol,
87(11):6346-58
210. Zoufaly A, Cramer JP, Vettorazzi E, Sayk F,
Bremer JP, Koop I, de Weerth A, Schmiedel S,
Jordan S, Fraedrich K, Asselborn NH, Nitschke
M, Neumann-Grutzeck C, Magnus T, Rüther
C, Fellermann K, Stahl RK, Wegscheider K,
Lohse AW (2013) Risk factors for development
of hemolytic uremic syndrome in a cohort of adult
patients with STEC 0104:H4 infection. PLOS ONE,
8(3):e59209
Publications
197. Weissbrich B, Nauerth M, Busch DH
(2013) Adoptive immunotherapy: New assay for the
identification of T cells with optimal avidity. Landes
Bioscience, 2(10):e26199
58
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