22/10/2013. antibiotic resistance an ecological problem. this part of the session. an ecological perspective. selection pressure and evolution

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1 antibiotic resistance an ecological problem Jon Iredell NHMRC Centre for Research Excellence in Critical Infection Marie Bashir Institute Westmead Millennium Institute 2 - the global bacterial ecosystem - optimising microbial husbandry - picking resistance early natural checks and balances - predator-prey balance: bacteriophages 3 4 1

2 shared bacteria connect us all - the global bacterial ecosystem that keeps us healthy - microbial husbandry - the consequences of late recognition natural checks and balances - predator-prey balance: bacteriophages drinking and bathing waters animals travel 5 6 the global bacterial gene pool: bacteria share genes between each other - the global bacterial ecosystem - microbial husbandry - picking resistance early natural checks and balances - predator-prey balance: bacteriophages rules of the gene pool: R gene/s/ R plasmids shared gene pools Only one gene carrier of each type per bacteria (plasmid incompatibility) Once carriers are in, they stay in (plasmid addiction) 7 8 2

3 (gut) bacterial community the silent majority dynamic and responsive, complex relationship to the immune system, stable average state resistant to outside influences, including diet. Bacteria we hit. Bacteria we aim at 9 10 AMP/MTZ antimicrobial stewardship: good microbial husbandry major types of bacteria Good bugs (?) Good bugs Bad bugs Other bugs 3GC antibiotics with small ecological footprints minimising antibiotic exposure repairing ecological damage: probiotics Doing the same experiment with humans in ICU: Comparing good drug and bad drug that are equally effective against the bugs we aim at Paradox: bad drug leads to more of the bugs we aim at! (opportunists) Probiotics Probiotics should work - some probably do They might keep some bugs out of ICU Not enough research so we have to make do Seems Nan was right there s nothing like a healthy

4 immediate - the global bacterial ecosystem survival delayed - microbial husbandry What it is - picking resistance early natural checks and balances How to treat it - predator-prey balance: bacteriophages Crit Care Resusc ABS. Cancer in Australia 2005 J Infect Dis Crit Care Med Am J Cardiol the global bacterial gene pool: bacteria share genes between each other E. coli gene sharing bacteria that normally live in us K. pneumoniae S. pneumoniae S. aureus >90% In Sydney, for the major causes of life-threatening infection, we can identify antibiotic susceptibility with >99.5% reliability 15 rules of the gene pool: R gene/s/ R plasmids shared gene pools Only one gene carrier of each type per bacteria (plasmid incompatibility) Once carriers are in, they stay in (plasmid addiction) The best adapted gene packages win! 16 4

5 - the global bacterial ecosystem - microbial husbandry - picking resistance early natural checks and balances - predator-prey balance: bacteriophages natural predators bacteriophage: viruses that prey on bacteria

6 - the global bacterial ecosystem - microbial husbandry - picking resistance early system balance and imbalance - predator-prey balance: phages and immunity eg for: Golden staph (MRSA etc) Pseudomonas (eg in Cystic Fibrosis) the global bacterial gene pool: bacteria share genes between each other Plasmid incompatibility: only one plasmid of each type at a time X R (bad) plasmid will outcompete S (good) plasmid if antibiotic provides an advantage X plasmid stability in absence of antibiotic selection is provided by addiction systems rules of the gene pool: R gene/s/ R plasmids shared gene pools Only one gene carrier of each type per bacteria (plasmid incompatibility) Once carriers are in, they stay in (plasmid addiction)

7 Plasmid addiction: plasmid produces stable toxin and unstable antidote Both daughter cells are full of long-lived stable toxin addictive R (bad) plasmid with toxin and antitoxin The plasmid continues to provide the short-lived antidote Cells without the plasmid (antidote) die. curative plasmid challenges both addiction and compatibility Getting rid of the antibiotic resistance: making bacteria susceptible stopping transmission spread?rescuing biodiversity Research Activity Domains (RADs) Major human diseases Major animal diseases Microbiome disturbance Antimicrobial resistance Pandemic infections Zoonoses Transmission Environment & Sustainability Biosecurity

8 2009 Maldives cabinet meeting thanks Funding: - National Health and Medical Research Council of Australia - NHMRC Centre for Research Excellence in Critical Infection Key affiliations: - Marie Bashir Institute - Westmead Millennium Institute - Sydney Medical School - More information? - type critical infection into your browser - sydney.edu.au/medicine/criticalinfection/

9 the golden staph Gram neg the paradox of gut bacteria Gram pos (S. aureus) - common infections - infected cuts (surgery) - boils and impetigo - bone and joint - survival strategies - drying - physical stress (E. coli): - normal gut ecology - commonest cause of lethal blood infection - less hardy - all about sharing - messages - rapid and efficient gene exchange Gram staining indicates basic differences 1880s: Streptococcus or Klebsiella pneumoniae? Gram pos Gram neg Hans Christian Joachim Gram ( )

10 Darwinian evolution: successful mutations are passed on Recombinant evolution: rapid and promiscuous gene exchange sampling the outside world Gram pos Tend to be more hardy and resistant to drying not ideally adapted to the aqueous environment typically cant swim Gram neg sensing and responding single outer wall Information exchange - chemical messages - genetic material

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