Evolving Antibiotics and other Fairy Tales The Quest for the “Perfect Antibiotic” by Chris Engdahl

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  • Slide 1
  • Evolving Antibiotics and other Fairy Tales The Quest for the Perfect Antibiotic by Chris Engdahl
  • Slide 2
  • Antibiotic Resistance Mutations create novel antibiotic antagonists (-lactamase)Mutations create novel antibiotic antagonists (-lactamase) Strong selective pressures (i.e. antibiotics) eliminate nonresistant strainsStrong selective pressures (i.e. antibiotics) eliminate nonresistant strains Interspecies competition promotes virulence factorsInterspecies competition promotes virulence factors Those strains immune survive to reproduceThose strains immune survive to reproduce
  • Slide 3
  • Antibiotic Resistance Methicillin-resistant Staph. aureus (MRSA) Vancomycin-resistant enterococcus (VRE) Streptococcus pneumoniae Salmonella Campylobacter Pseudomonas aeruginosa (Burn victims) Escherichia coli And many, many more
  • Slide 4
  • Antibiotic Resistance Graphic example of natural selection and evolution in action Novel antibiotics quickly lose efficacy New resistant strains emerge fast
  • Slide 5
  • Are We Screwed? (Perhaps not)
  • Slide 6
  • Ganges River, 1896 Considered a dirty river Bacteriologist Ernest Hankin determines an unfilterable antimicrobial agent preventing cholera outbreaks
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  • Paris, 1917 Flix d'Hrelle discovers "an invisible, antagonistic microbe of the dysentery bacillus ... a virus parasitic on bacteria. Call his discovery a bacteriophage (bacteria-eater) Forgotten to Western Medicine with the Antibiotic Revolution (but not to Russia)
  • Slide 8
  • Enter the Phage Bacterias Natural Predator 910 8 virions/mm in oceans Arguably the most abundant life form on earth Infects 70% of marine bacteria
  • Slide 9
  • Bacteriophage Life Cycle
  • Slide 10
  • Phage antagonists exist for the following pathogens Corynebacterium diphtheriaeCorynebacterium diphtheriae Listeria monocytogenesListeria monocytogenes Escherichia coliEscherichia coli Salmonella typhiSalmonella typhi Multidrug Resistant Staphylococcus Areus (MRSA)Multidrug Resistant Staphylococcus Areus (MRSA) Streptococcus pneumoniaeStreptococcus pneumoniae Pseudomonas aeruginosaPseudomonas aeruginosa Shigela dysenteriaeShigela dysenteriae Vibrio choleraeVibrio cholerae Klebsiella pneumoniaeKlebsiella pneumoniae Clostridium perfringensClostridium perfringens
  • Slide 11
  • Benefits of Phage Therapy Target specificTarget specific Quick, easy, and cheap to growQuick, easy, and cheap to grow Evolving antibioticEvolving antibiotic No documented side effects (GRAS organisms)No documented side effects (GRAS organisms)
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  • Shortcomings Body may mount immune response, decreasing efficacyBody may mount immune response, decreasing efficacy Not all bacteria have a phage antagonist yetNot all bacteria have a phage antagonist yet Public perceptionPublic perception Traditional stereotypes (Russian)Traditional stereotypes (Russian) Ineffective against viral infectionsIneffective against viral infections
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  • In Summary Phage Therapy is a novel, effective and evolving treatment for many bacterial infectionsPhage Therapy is a novel, effective and evolving treatment for many bacterial infections Largely untested due to public perception (live virus syndrome) and Cold War politicsLargely untested due to public perception (live virus syndrome) and Cold War politics Potential for genetic manipulation and enhancementPotential for genetic manipulation and enhancement Some Phase 1 clinical trials in progress now in Lubbock, TXSome Phase 1 clinical trials in progress now in Lubbock, TX FDA approved for meat processing against Listeria monocytogenesFDA approved for meat processing against Listeria monocytogenes
  • Slide 14
  • Bibliography Articles Brssow H "Phage therapy: the Escherichia coli experience. Microbiology (2005) v. 151, p.2133-2140.Brssow H "Phage therapy: the Escherichia coli experience. Microbiology (2005) v. 151, p.2133-2140. Soothill JS (1994). "Bacteriophage prevents destruction of skin grafts by Pseudomonas aeruginosa". Burns 20 (3): 20911.Soothill JS (1994). "Bacteriophage prevents destruction of skin grafts by Pseudomonas aeruginosa". Burns 20 (3): 20911. Duckworth DH, Gulig PA (2002). "Bacteriophages: potential treatment for bacterial infections". BioDrugs 16 (1): 5762.Duckworth DH, Gulig PA (2002). "Bacteriophages: potential treatment for bacterial infections". BioDrugs 16 (1): 5762. Pirisi A (2000). "Phage therapyadvantages over antibiotics?". Lancet 356 (9239): 1418.Pirisi A (2000). "Phage therapyadvantages over antibiotics?". Lancet 356 (9239): 1418. "Stalin's Forgotten Cure" Science 25 October 2002 v.298"Stalin's Forgotten Cure" Science 25 October 2002 v.298 Thiel, Karl (January 2004). "Old dogma, new tricks21st Century phage therapy". Nature Biotechnology (London UK: Nature Publishing Group) 22 (1): 3136.Thiel, Karl (January 2004). "Old dogma, new tricks21st Century phage therapy". Nature Biotechnology (London UK: Nature Publishing Group) 22 (1): 3136. Wommack KE, Colwell RR (March 2000). "Virioplankton: viruses in aquatic ecosystems". Microbiol. Mol. Biol. Rev. 64 (1): 69114.Wommack KE, Colwell RR (March 2000). "Virioplankton: viruses in aquatic ecosystems". Microbiol. Mol. Biol. Rev. 64 (1): 69114.Hyperlinks http://www.cfsan.fda.gov/~rdb/opa-g198.html - FDA Agency Response Letter GRAS Notice No. GRN 000198http://www.cfsan.fda.gov/~rdb/opa-g198.html - FDA Agency Response Letter GRAS Notice No. GRN 000198http://www.cfsan.fda.gov/~rdb/opa-g198.html http://www.youtube.com/watch?v=9hzUjx_oD8E - Bacteriophage life cycle a la Youtubehttp://www.youtube.com/watch?v=9hzUjx_oD8E - Bacteriophage life cycle a la Youtubehttp://www.youtube.com/watch?v=9hzUjx_oD8E http://www.phage.ulaval.ca/index.php?pageDemandee=1 - Flix d'Hrelle Reference Center for Bacterial Viruseshttp://www.phage.ulaval.ca/index.php?pageDemandee=1 - Flix d'Hrelle Reference Center for Bacterial Viruseshttp://www.phage.ulaval.ca/index.php?pageDemandee=1 www.phagetherapycenter.com/ - Phage Therapy Center of Tbilsi, Georgia. effective treatment solution for patients who have bacterial infections that do not respond to conventional antibioticswww.phagetherapycenter.com/ - Phage Therapy Center of Tbilsi, Georgia. effective treatment solution for patients who have bacterial infections that do not respond to conventional antibioticswww.phagetherapycenter.com/