Download We are in an arms race

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
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Methicillin-resistant Staph. aureus (MRSA)
Vancomycin-resistant enterococcus (VRE)
Streptococcus pneumoniae
Salmonella
Campylobacter
Pseudomonas aeruginosa (Burn victims)
Escherichia coli
And many, many more…
Antibiotic Resistance
• Graphic example of
natural selection
and evolution in
action
• Novel antibiotics
quickly lose efficacy
• New resistant
strains emerge fast
Are We Screwed?
(Perhaps not…)
Ganges River, 1896
• Considered a dirty
river
• Bacteriologist Ernest
Hankin determines
an unfilterable
antimicrobial agent
preventing cholera
outbreaks
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
• 9×108 virions/mm in
oceans
• Arguably the most
abundant life form
on earth
• Infects 70% of
marine bacteria
Bacteriophage Life Cycle
Phage antagonists
exist for the following
pathogens
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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
Benefits of
Phage Therapy
• Target specific
• Quick, easy, and
cheap to grow
• “Evolving antibiotic”
• No documented side
effects (GRAS
organisms)
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
• 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
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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”