Evolving Antibiotics and other Fairy Tales The Quest for the “Perfect...

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Evolving Antibiotics and other Fairy Tales The Quest for the “Perfect Antibiotic” by Chris Engdahl. Antibiotic Resistance. Mutations create novel antibiotic antagonists ( β -lactamase) Strong selective pressures (i.e. antibiotics) eliminate nonresistant strains - PowerPoint PPT Presentation

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  • Evolving Antibiotics and other Fairy Tales

    The Quest for the Perfect Antibioticby Chris Engdahl

  • Antibiotic ResistanceMutations create novel antibiotic antagonists (-lactamase)Strong selective pressures (i.e. antibiotics) eliminate nonresistant strainsInterspecies competition promotes virulence factorsThose strains immune survive to reproduce

  • Antibiotic ResistanceMethicillin-resistant Staph. aureus (MRSA) Vancomycin-resistant enterococcus (VRE)Streptococcus pneumoniae SalmonellaCampylobacterPseudomonas aeruginosa (Burn victims)Escherichia coli And many, many more

  • Antibiotic ResistanceGraphic example of natural selection and evolution in actionNovel antibiotics quickly lose efficacyNew resistant strains emerge fast

  • Are We Screwed?(Perhaps not)

  • Ganges River, 1896Considered a dirty river Bacteriologist Ernest Hankin determines an unfilterable antimicrobial agent preventing cholera outbreaks

  • Paris, 1917Flix 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)

  • Enter the PhageBacterias Natural Predator9108 virions/mm in oceansArguably the most abundant life form on earthInfects 70% of marine bacteria

  • Bacteriophage Life Cycle

  • Phage antagonists exist for the following pathogens

    Corynebacterium diphtheriae Listeria monocytogenesEscherichia coliSalmonella typhiMultidrug Resistant Staphylococcus Areus (MRSA)Streptococcus pneumoniae Pseudomonas aeruginosa Shigela dysenteriae Vibrio choleraeKlebsiella pneumoniaeClostridium perfringens

  • Benefits of Phage TherapyTarget specificQuick, easy, and cheap to growEvolving antibioticNo documented side effects (GRAS organisms)

  • ShortcomingsBody may mount immune response, decreasing efficacyNot all bacteria have a phage antagonist yetPublic perceptionTraditional stereotypes (Russian)Ineffective against viral infections

  • In SummaryPhage Therapy is a novel, effective and evolving treatment for many bacterial infections

    Largely untested due to public perception (live virus syndrome) and Cold War politics

    Potential for genetic manipulation and enhancement

    Some Phase 1 clinical trials in progress now in Lubbock, TX

    FDA approved for meat processing against Listeria monocytogenes

  • BibliographyArticlesBrssow 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. 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."Stalin's Forgotten Cure" Science 25 October 2002 v.298Thiel, 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.

    Hyperlinks http://www.cfsan.fda.gov/~rdb/opa-g198.html - FDA Agency Response Letter GRAS Notice No. GRN 000198http://www.youtube.com/watch?v=9hzUjx_oD8E - Bacteriophage life cycle a la Youtubehttp://www.phage.ulaval.ca/index.php?pageDemandee=1 - Flix d'Hrelle Reference Center for Bacterial Viruses www.phagetherapycenter.com/ - Phage Therapy Center of Tbilsi, Georgia. effective treatment solution for patients who have bacterial infections that do not respond to conventional antibiotics