Download People

Bacterial infection and antibiotics
Laboratory of Microbial Pathogens
and Antimicrobial Therapy
（病原微生物与抗感染治疗课题组）
Established in December 2012
Xilin Zhao, Ph.D., Professor
Dai Wang, Ph.D., Associate Professor
School of Public Health, Xiamen University
People
•
Group leader
Prof. Xilin Zhao，Ph.D
•
Group member
Dr. Dai Wang, Assoc. Prof.
Dr. Yiqun Liao, Assist. Prof.
Ms. Yunxin Xue, Assist. Eng.
•
Postgraduate Student
Ms. Jinzhi Feng
Ms. Lina Ma
Contact us：
Tel：+86（0）592-2880630
Email：[email protected]; [email protected]
Bacterial infection
Pathogenesis
Antimicrobial resistance
New antimicrobials
New antimicrobial enhancers
Bacterial apoptosis
Bacterial stress response
Virulence factors
Xilin Zhao
B.S./M.S. (Nankai Univ.)
Ph.D. (Univ. East Anglia/
John Innes Centre, UK)
Bacterial stress response and
programmed cell death
Mechanisms of antimicrobial killing
Antimicrobial resistance
Tuberculosis
http://www.phri.org/research/res_pizhao.asp
Dai Wang
B.S. (Shanghai Univ.)
M.S./Ph.D. (Univ. Edinburgh, UK)
Bacterial pathogenesis
Type III secretion system
Yiqun Liao
B.S./M.S./Ph.D. (Xiamen Univ.)
Molecular diagnosis
HBV Drug resistance
Bacterial microRNA
Bacterial infection is a leading
cause of infectious diseases
In the past 70 years, 335 human infectious diseases have been
discovered, more than half are caused by bacterial infection.
Tuberculosis: 10 million new cases per year, ~2 million death
Bacterial pneumonia: 4.5 million cases a year, 60,000 death (US)
Cholera: 5.5 million cases a year, 130,000 death.
Black death (Plaque) caused by Yersinia pestis infection
killed 75 to 200 million, about half of European population.
Spontaneous generation v.s.
the germ theory of disease
Spontaneous generation was coherently synthesized by Aristotle
different types of life might repeatedly emerge from specific
sources other than seeds, eggs or parents.
life routinely emerges from non-living matter on a time scale of
anything from minutes to weeks (mice and other animals arise
from the mud of the Nile; aquatic forms being produced directly
from lifeless matter)
The germ theory of disease refers to the discovery in the late
19th century that some infectious diseases are caused by
microorganisms, small organisms too small to see without
magnification, that invade the host.
Significant contributors of
the germ theory of disease
Significant contributors of
the germ theory of disease
Bacteria were first discovered
by Antonie Philips van
Leeuwenhoek in the 1670s
Discovered germ theory of fermentation
He is considered as the
“Father of Microbiology”
since he used handcrafted
microscopes to first observed
many different single celled
organisms.
Created the first vaccine
Invented pasteurization for sterilization
Louis Pasteur
Significant contributors of
the germ theory of disease
Koch's Four Postulates
Founder of modern bacteriology
1. The organism must always be present, in every case of the
disease.
Identified the specific causative agents of
tuberculosis, cholera, and anthrax
2. The organism must be isolated from a host containing the
disease and grown in pure culture.
Created the Koch’s postulates for linking
specific microorganisms to particular diseases
3. Samples of the organism taken from pure culture must cause
the same disease when inoculated into a healthy,
susceptible animal in the laboratory.
Invented multiple methods for culturing pure
bacteria (Potato slice, gelatin, agar)
Robert Koch
4. The organism must be isolated from the inoculated animal
and must be identified as the same original organism first
isolated from the originally diseased host.
Significant contributors of
the germ theory of disease
Transmittable infectious diseases used
to be the leading cause of human death
The 1918 Spanish Flu:
Pioneered antiseptic surgery
Infected 500 million people and killed 50-100 million
Bad air or bacterial transmission
Unlike most other influenza outbreaks that disproportionately
kill juvenile, elderly, or already weakened patients; the 1918
pandemic killed predominantly previously healthy young adults.
Filtration, exposure to heat, exposure to
chemicals
Carbolic acid (now known as phenol)
Joseph Lister
The majority of deaths were from bacterial pneumonia, but the
virus also killed people directly, causing massive hemorrhages
and edema in the lung.
Ended the World War I due to lack of troops supply
Tuberculosis
Characteristics of M. tuberculosis
 Slow growing

Bacterial infection caused by
Mycobacterium tuberculosis

Damages lungs or other parts of the body
 Waxy cell wall

Fatal if not treated properly
 Refractory to
chemotherapy
 High bacterial
burden
cholera
The challenge for tuberculosis control
Caused by vibrio cholerae infection (O1, and O139)
 A third of human population are infected,
~10 million new cases (~2 million deaths) per year.
Transmits through contaminated food and water
 Slow growing pathogen, high bacterial burden, dormancy.
3-5 million cases, 130,000 death in 2010
 Long treatment time with multiple agents required.
Used to be a much deadly disease, killing tens of millions
in 19th century
 Increasing prevalence of MDR, XDR, and CDR cases.
7 cholera pandemics have occurred in the past 200 years,
with the seventh originating in Indonesia in 1961.
Plague (Black death)
Occurred during 1348–1350
Caused by Yersinia pestis infection
THE 10 LEADING CAUSES OF DEATH AS A PERCENTAGE
OF ALL DEATHS, U.S 1900 - 1997
Pnuemonia
Tuberculosis
Diarrhea and Enteritis
Heart disease
Stroke
1900
40% of all deaths
Liver disease
started in China or central Asia and travelled along the Silk Road
and reached the Europe by 1346
Injuries
Cancer
Senility
Diphtheria
Killed 75-200 million or near half of European population
2 other major outbreaks of had been occurred:
Heart disease
Cancer
Stroke
The Plague of Justinian in the 6th and 7th centuries,
wiped out half of European population
Lung disease
Injuries
Pnuemonia & Influenza
Diabetes
HIV
Suicide
China and India in the 1890s, also killed millions.
Liver disease
1997
5% of total
The Decline of Infectious Diseases
1. Increased hygiene and sanitation
(chlorinated drinking water, sewage treatment etc.)
2. Antibiotics
3. Childhood vaccination programs
History of antibiotic discovery
Year
Origin
1640
England John Parkington recommended using mold for treatment in his book on
pharmacology
1870
England
Sir John Scott Burdon-Sanderson observed that culture fluid covered with
mould did not produce bacteria
1871
England
Joseph Lister experimented with the antibacterial action on human tissue on
what he called Penicillium glaucium
1875
England
John Tyndall explained antibacterial action of the Penicillium fungus to the
Royal Society
1877
France
Louis Pasteur postulated that bacteria could kill other bacteria (anthrax bacilli)
1897
France
Ernest Duchesne healed infected guinea pigs from typhoid using mould
(Penicillium glaucium)
1928
England
Sir Alexander Fleming discovered enzyme lysozyme and the antibiotic
substance penicillin from the fungus Penicillium notatum
1932
Germany
Gerhard Domagk discovered Sulfonamidochrysoidine (Prontosil )
1943
USA
DEFINITIONS
Antibiotic:
compound produced by a microorganism that kills
or inhibits the growth of another microorganism.
Antimicrobial:
Antibiotics and synthetic compounds that kills or
block the growth of microorganisms including
bacteria, fungi, viruses, and even protozoans.
History of antimicrobial discovery
Description
Selman Waksman discovered streptomycin
Paul Ehrlich: father of chemotherapy, initiated the concept of
chemotherapy (1904), discovered Salvarsan (1910) for the
protozoal disease sleeping sickness.
Prontosil (Gerhard Domagk, 1932, 1935) against streptococcal
infections, later recognized as a prodrug for the first class
of true antibacterial—Sulfonamides
Penicillin: first true antibiotic, discovered 1928 by Alexander
Fleming but not widely used clinically until 1940.
Streptomycin: Selman Waksman
Additional reading materials:
http://www.chem.msu.su/rus/books/patrick/part2.pdf
http://www.experiment-resources.com/history-of-antibiotics.html
The initiation of the concept of chemotherapy
The Discovery of Sulfonamides
The father of chemotherapy
In 1932, Gerhard Domagk discovered that a red
dye, called prontosil rubrum, protected mice and
rabbits against lethal doses of staphylococci and
haemolytic streptococci.
Initiated the concept of chemotherapy (1904)
Discovered Salvarsan (1910) for the
protozoal disease sleeping sickness
and syphilis.
Won Nobel price for his work on acquired
Immunity in 1908
Paul Ehrlich
Pioneered antiseral valency standards.
Prontosil was a derivative of sulphanilamide
(p-aminobenzenesulphonamide), which the
Viennese chemist, Gelmo, had synthesized in
1908.
Gerhard Domagk
In 1935, Prontosil was shown clinically effective
against streptococcal infection, landing Domagk
Nobel Price in 1939.
Coined the concept of “magic bullet”.
Discovered the existence of blood-brain barrier.
Discovery of penicillin
The Discovery of streptomycin
Staphyloccus aureus
Father of antibiotic, a word he coiled.
Penicillin
Fungus: Penicillium
notatum
Ernest Duchesne
Andrew J. Moyer
Sir Alexander Fleming Ernst Chain Sir Howard Florey
The Nobel Prize in Physiology or Medicine 1945
"for the discovery of penicillin and its curative effect in various infectious diseases".
Discovered streptomycin, neomycin, and
>15 other antibiotics
Noble price in 1952 for his discovery of
streptomycin, the first antibiotic effective
against tuberculosis
Controversy about proper credit for
streptomycin discovery with his student,
Albert Schatz.
Selman Waksman
The mission of scientist
Uncover the law and truth of mother nature
A quiz
1. Which month has 28 days?
Persist (truth often lies in the hands of minority)
2. What can’t you ever grab with your right hand?
Challenge authority (Respect law of nature more than respect
any person
3. How many eggs can you eat with an empty stomach?
Comprehensive (no rush to conclusion, self-correct)
Unlimited imagination
Suggested reading: “The structure of Scientific Revolutions by
Thomas S. Kuhn
4. Can you imagine something that might travel faster than light?