1. Antibiotic Resistance Workshop

2. 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. 2 Trends in antibiotic resistance (invasive infections), 2002-2008. Source: European Antimicrobial Resistance Surveillance System (EARSS), 2009.

3. 20022007 Methicillin-resistant Staphylococcus aureus (MRSA), blood and spinal fluid No data <1% 1-5% 5-10% 10-25% 25-50% >50% Source: European Antimicrobial Resistance Surveillance System (EARSS), 2008. 3

4. Misuse of antibiotics drives antibiotic resistance Studies prove that misuse of antibiotics may cause patients to become colonised or infected with antibiotic- resistant 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

5. How drug resistance spreads

6. Reduced drug discovery

7. 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.

8. 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

9. 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 14.00Introduction & welcome 14.20Introductions Each person to present their research and interest in Antibiotic Resistance (Max 5 mins each) 15.20Refreshment break and further networking Opportunity for all to put their ‘Wants’ and ‘Offers’ on the board 15.50Potential Projects Informal session to discuss potential collaborations and projects. 17.00 Wrap up and close

10. What happens when antibiotics are added to bacteria ? Time Number of viable bacteria Bacterial population exposed to high doses of an antibiotic This fraction survive

11. Bigger et al., 1944

12. How do persister cells form ? If key cellular processes are blocked then antibiotics are ineffective

13. 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

14. 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 down- regulated genes. Functional categories were assigned according to the Burkholderia Genome Database.