Evolving antibiotics and other fairy tales the quest for the perfect antibiotic by chris engdahl
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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

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

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Evolving antibiotics and other fairy tales the quest for the perfect antibiotic by chris engdahl

Evolving Antibioticsand other Fairy TalesThe Quest for the “Perfect Antibiotic”by Chris Engdahl


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

  • Interspecies competition promotes virulence factors

  • Those strains immune survive to reproduce


Antibiotic resistance

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…


Evolving antibiotics and other fairy tales the quest for the perfect antibiotic by chris engdahl

Antibiotic Resistance

  • Graphic example of natural selection and evolution in action

  • Novel antibiotics quickly lose efficacy

  • New resistant strains emerge fast


Evolving antibiotics and other fairy tales the quest for the perfect antibiotic by chris engdahl

Are We Screwed?

(Perhaps not…)


Ganges river 1896

Ganges River, 1896

  • Considered a dirty river

  • Bacteriologist Ernest Hankin determines an unfilterable antimicrobial agent preventing cholera outbreaks


Paris 1917

Paris, 1917

  • Félix d'Hérelle 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 phage bacteria s natural predator

Enter the PhageBacteria’s Natural Predator

  • 9×108 virions/mm in oceans

  • Arguably the most abundant life form on earth

  • Infects 70% of marine bacteria


Bacteriophage life cycle

Bacteriophage Life Cycle


Phage antagonists exist for the following pathogens

Corynebacterium diphtheriae

Listeria monocytogenes

Escherichia coli

Salmonella typhi

Multidrug Resistant Staphylococcus Areus (MRSA)

Streptococcus pneumoniae

Pseudomonas aeruginosa

Shigela dysenteriae

Vibrio cholerae

Klebsiella pneumoniae

Clostridium perfringens

Phage antagonists exist for the following pathogens


Benefits of phage therapy

Benefits of Phage Therapy

  • Target specific

  • Quick, easy, and cheap to grow

  • “Evolving antibiotic”

  • No documented side effects (GRAS organisms)


Shortcomings

Shortcomings

  • Body may mount immune response, decreasing efficacy

  • Not all bacteria have a phage antagonist …yet

  • Public perception

  • Traditional stereotypes (Russian)

  • Ineffective against viral infections


In summary

In Summary

  • Phage 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


Bibliography

Bibliography

Articles

  • Brüssow 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): 209–11.

  • Duckworth DH, Gulig PA (2002). "Bacteriophages: potential treatment for bacterial infections". BioDrugs 16 (1): 57–62.

  • Pirisi A (2000). "Phage therapy—advantages over antibiotics?". Lancet 356 (9239): 1418.

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

  • Thiel, Karl (January 2004). "Old dogma, new tricks—21st Century phage therapy". Nature Biotechnology (London UK: Nature Publishing Group) 22 (1): 31–36.

  • Wommack KE, Colwell RR (March 2000). "Virioplankton: viruses in aquatic ecosystems". Microbiol. Mol. Biol. Rev. 64 (1): 69–114.

    Hyperlinks

  • http://www.cfsan.fda.gov/~rdb/opa-g198.html - FDA Agency Response Letter GRAS Notice No. GRN 000198

  • http://www.youtube.com/watch?v=9hzUjx_oD8E - Bacteriophage life cycle a la Youtube

  • http://www.phage.ulaval.ca/index.php?pageDemandee=1 - Félix d'Hérelle 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”


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