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Antibiotic Resistance
Workshop
Antibiotic resistance –
a problem in the present and the future
• Antibiotic resistance is an increasingly serious public health problem:
resistant bacteria have become an everyday concern in hospitals
across Europe.
Proportion of resistant isolates (%)
30
20
10
0
2002
2003
2004
2005
2006
2007
2008
Penicillin-non susceptible S. pneumoniae (EU pop.-weighted average)
Erythromycin-resistant S. pneumoniae (EU pop.-weighted average)
Fluoroquinolone-resistant E. coli (EU pop.-weighted average)
Third-gen. cephalosporin-resistant E. coli (EU pop.-weighted average)
2
Trends in antibiotic resistance (invasive infections), 2002-2008. Source: European
Antimicrobial Resistance Surveillance System (EARSS), 2009.
Methicillin-resistant Staphylococcus
aureus (MRSA), blood and spinal fluid
2002
2007
No data
<1%
1-5%
5-10%
10-25%
25-50%
>50%
Source: European Antimicrobial Resistance Surveillance System (EARSS), 2008.
3
Misuse of antibiotics drives
antibiotic resistance
• Studies prove that misuse of antibiotics may cause
patients to become colonised or infected with antibioticresistant bacteria, such as methicillin-resistant
Staphylococcus aureus (MRSA), vancomycin-resistant
enterococci (VRE) and highly-resistant Gram-negative
bacilli.
• Misuse of antibiotics is also associated with an increased
incidence of Clostridium difficile infections.
4
How drug resistance spreads
Reduced drug discovery
How to address these problems
•
•
•
improve the knowledge and
understanding of antimicrobial
resistance,
conserve and steward the
effectiveness of existing treatments,
stimulate the development of new
antibiotics, diagnostics and novel
therapies.
Initiatives to address these
problems
•
•
•
•
MRC – strategic priority
BBSRC – to announce call this year
Wellcome
NIHR Themed Call: Preventing the
development and spread of antimicrobial
resistance
Aims:
To bring together researchers from across the university with an interest in
Antibiotic Resistance to identify unifying research themes and discuss the
potential for joint projects; to explore ideas ready for future MRC grant funding
calls.
AGENDA
14.00
Introduction & welcome
14.20
Introductions
Each person to present their research and interest in Antibiotic Resistance
(Max 5 mins each)
15.20
15.50
17.00
Refreshment break and further networking
Opportunity for all to put their ‘Wants’ and ‘Offers’ on the board
Potential Projects
Informal session to discuss potential collaborations and projects.
Wrap up and close
What happens when antibiotics
are added to bacteria ?
Number of viable bacteria
Bacterial population exposed to high doses of an antibiotic
This fraction
survive
Time
Bigger et al., 1944
How do persister cells form ?
If key cellular processes are blocked then
antibiotics are ineffective
Toxin-Antitoxin (TA) Modules
•Units of long-lived toxin and short-lived antitoxin
•Toxin causes growth arrest by targeting different essential cell
processes
•Antitoxin neutralizes toxic activity by forming a heterodimeric
complex
Gerdes et al. (2005) Nat. Rev. Microbiol. 3:371-382
A)
B)
Functional classification
of differentially regulated
genes in persister cells.
RNAseq comparison
between persister cells (24
hrs incubation with 100x
MIC ceftazidime) and cells
grown in LB medium to
mid-log phase (A) or
stationary phase (B).
Green bars represent
genes that were
upregulated in persisters;
red bars represent downregulated genes.
Functional categories were
assigned according to the
Burkholderia Genome
Database .