Evolving Antibiotics and other Fairy Tales The Quest for the â€œPerfect...
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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