Phage Therapy

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Phage Therapy
Dr. Ira Presser
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Bacteriophage lambda life cycle (a
temperate phage)
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Disadvantages of Antibiotics

• Emergence of multiple resistant strains
• Induction of secondary infections due to changes
  in normal flora
• Legislation against prophylactic use in animals

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Alternatives to Antibiotics

• Antimicrobial peptides (e.g. maigainins,
  defensins drosocin)
• Probiotics (Nisin, bacteriosins microsins)
• Vaccination
• Phage therapy

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Phage morphology
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History of phage therapy

• Hankin (1896) reported that waters of Ganges had
  filterable anti-cholera activity which was
  destroyed by heating
• DHerelle (1917) isolated filterable
  anti-Shigella microbe that could lyse Shigella in
  vitro.

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• Next 50 years results were inconclusive This can
  be attributed to
• 1. The failure to select high virulent phages
• 2. The use of phages to combat a mixed
  infection
• 3. Emergence of resistant strains of bacteria-
  use multiple phage strains
• 4. Failure to neutralize gastric pH prior to
  administration
• 5. Liberation of endotoxins

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• Most current work was developed in Tbsilli,
  Georgia
• They have developed strains that have inhibited
  gt70 of the specific pathogenic strains tested.
  (Staph, Pseudomonas, E. coil, Proteus.
• Work in Britain developed a coli phage that
  although was not specific for K99 fimbriae could
  significantly stop fluid loss reduce bacterial
  count several orders of magnitude.

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• Phages can protect guinea pigs against infection
  with Pseudomonas. 100 phages can protect against
  challenge with 106 bacteria (5x LD50)

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Advantages of Phage Therapy

• They are both self-replicating and self-limiting.
  
• Repeated administration unlikely, as long as
  target bacteria present, phage will reproduce
• Renders herd immunity
• More specifically targeted than antibiotics.
• Unlike antibiotics in which concentration
  decreases after inoculation, the phage
  concentration increases
• Does not upset normal flora that can lead to
  secondary infections
• Can be administered prophylactically to prevent
  bacterial disease
• Use to control Salmonella contamination either
  before slaughter or on carcasses

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Referenceswww.phagetherapycenter.com

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• E-coli.

Electron micrograph of phage courtesythe
Australian National University
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References

1. Wagenaar, et. al. Phage therapy reduces
   Campylobacter jejuni colonization in broilers.
   Vet. Microbiol. 109275 (2005).
2. Goode, et. al., Reduction in Experimental
   Salmonella Campylobacter Contamination of
   Chicken Skin by Application of lytic
   Bacteriophages, Applied Enviorn. Micro. 695036
   (2003)

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References Cont

• 3. Higgins et. al. Use of specific bacteriophages
  to reduce Salmonella in poultry products.
• 4. Fiorentin et.al., Oral treatment with
  bacteriophages reduces the concentration of S.
  Enteridis PT4 in caecal contents of broilers.
  Avian Pathol. 34259 (2005)
• 5. Barrow, Use of lytic bacteriophage for control
  of E.coli Septicemia Meningitis in Chickens
  Calves. Clin. Diagnostic Lab. Immunol. 5294
  (1998).

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References cont

• 6. OFlynn et.al., Evaluation of a Cocktail of 3
  Bacteriophages for Biocontrol of E. coli O157H7.
  Applied Enviorn. Microb. 703417 (2004).
• 7. Huff, et.al. Therapeutic efficacy of
  bacteriophage Baytril individually in
  combination to treat colibacillosis. Poultry
  Science 831944 (2004).
• 8. Huff, et. al., Alternatives to antibiotics
  utilization of bacteriophages to treat
  colibacillosis prevent food borne pathogens.
  Poultry Science 84659 (2004).