title: Endemic bacteriophages: a cautionary tale for evaluation of bacteriophage therapy and other interventions for infection control in animals.
abstract: BACKGROUND
  One of the most effective targets for control of zoonotic foodborne pathogens in the farm to fork continuum is their elimination in food animals destined for market. Phage therapy for Escherichia coli O157:H7 in ruminants, the main animal reservoir of this pathogen, is a popular research topic. Since phages active against this pathogen may be endemic in host animals and their environment, they may emerge during trials of phage therapy or other interventions, rendering interpretation of trials problematic.
  
  
  METHODS
  During separate phage therapy trials, sheep and cattle inoculated with 109 to 1010 CFU of E. coli O157:H7 soon began shedding phages dissimilar in plaque morphology to the administered therapeutic phages. None of the former was previously identified in the animals or in their environment. The dissimilar "rogue" phage was isolated and characterized by host range, ultrastructure, and genomic and proteomic analyses.
  
  
  RESULTS
  The "rogue" phage (Phage vB_EcoS_Rogue1) is distinctly different from the administered therapeutic Myoviridae phages, being a member of the Siphoviridae (head: 53 nm; striated tail: 152x8 nm). It has a 45.8 kb genome which is most closely related to coliphage JK06, a member of the "T1-like viruses" isolated in Israel. Detailed bioinformatic analysis reveals that the tail of these phages is related to the tail genes of coliphage lambda. The presence of "rogue" phages resulting from natural enrichments can pose problems in the interpretation of phage therapeutic studies. Similarly, evaluation of any interventions for foodborne or other bacterial pathogens in animals may be compromised unless tests for such phages are included to identify their presence and potential impact.
authors.affiliation: Public Health Agency of Canada, Laboratory for Foodborne Zoonoses, 110 Stone Road West, Guelph, ON, N1G 3 W4, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Kropinski
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Lingohr
authors.forename: Dianne M
authors.initials: DM
authors.lastname: Moyles
authors.forename: Shivani
authors.initials: S
authors.lastname: Ojha
authors.forename: Amanda
authors.initials: A
authors.lastname: Mazzocco
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: She
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Bach
authors.forename: Erica A
authors.initials: EA
authors.lastname: Rozema
authors.forename: Kim
authors.initials: K
authors.lastname: Stanford
authors.forename: Tim A
authors.initials: TA
authors.lastname: McAllister
authors.forename: Roger P
authors.initials: RP
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods*; D002213:Capsid / Q000648:ultrastructure; D002417:Cattle; D002418:Cattle Diseases / Q000628:therapy*; D003090:Coliphages / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000648:ultrastructure; D004927:Escherichia coli Infections / Q000628:therapy / Q000662:veterinary*; D019453:Escherichia coli O157 / Q000821:virology*; D016679:Genome, Viral; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D012756:Sheep; D012757:Sheep Diseases / Q000628:therapy*; D017906:Siphoviridae / Q000648:ultrastructure; D014764:Viral Proteins / Q000032:analysis
chemical_list: D014764:Viral Proteins