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Endemic bacteriophages: a cautionary tale for evaluation of bacteriophage therapy and other interventions for infection control in animals

Andrew M Kropinski12, Erika J Lingohr1, Dianne M Moyles2, Shivani Ojha1, Amanda Mazzocco1, Yi-Min She3, Susan J Bach4, Erica A Rozema567, Kim Stanford6, Tim A McAllister7 and Roger P Johnson1*

Author Affiliations

1 Public Health Agency of Canada, Laboratory for Foodborne Zoonoses, 110 Stone Road West, Guelph, ON, N1G 3 W4, Canada

2 Department of Molecular & Cellular Biology, University of Guelph, Guelph, ON, N1G 2 W1, Canada

3 Centre for Vaccine Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, ON, K1A 0 K9, Canada

4 Agriculture and Agri-Food Canada, Pacific Agri-Food Research Centre, Summerland, BC, V0H 1Z0, Canada

5 Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, T6G 2P5, Canada

6 Alberta Agriculture and Rural Development, Agriculture Centre, Lethbridge, AB, T1J 4 V6, Canada

7 Agriculture and Agri-Food Canada, Lethbridge Research Centre, Lethbridge, AB, T1J 4B1, Canada

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Virology Journal 2012, 9:207  doi:10.1186/1743-422X-9-207

Published: 17 September 2012

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: 152 x 8 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.

Keywords:
Escherichia coli O157:H7, VTEC; Phage therapy; Phage ecology; Genome; Proteome; Bioinformatics; Morphology; Electron microscopy