Project Summary

Isolation and Use of Bacteriophage to Reduce E. coli O157:H7 Populations in Ruminants

Principle Investigator(s):
Todd R. Callaway
U.S. Department of Agriculture, Agricultural Research Service
Completion Date:
Month 20--May 2005



Bacteria can be infected by bacterial viruses (bacteriophages, or phages). By nature, they are very specific such that an individual phage may only infect and subsequently kill a specific bacterial strain within a species. This high degree of specificity allows phages to be used against targeted microorganisms in a mixed population such as the ruminant gut without perturbing the microbial ecosystem. Bacteriophages are common natural members of the gastrointestinal microbial ecosystem of food animals, including ruminants (Adams et al., 1966; Klieve and Bauchop, 1988).  

Virulent bacteriophages attach to specific receptors on the surface of bacteria, inject their DNA, then express genes that “hijack” a bacterium; directing a transition from host to phage metabolism that leads to the synthesis of new phage DNA and new phage particles, ending with programmed cell lysis and the release of dozens or hundreds of new phage particles. This exponential increase in the number of phages continues if the targeted bacteria are present, thus allowing phages to persist in the gut rather than simply degrade over time as do antibiotics. Because phages are “infectious” agents, they can be passed between hosts, colonizing other animals and infecting the target bacteria in this new host; however, phages they are also self-limiting, if the target bacterium (prey) is removed from the environment, then the phage population, like any predator, will diminish. Ever since their discovery in 1917 they have been applied in both human and animal therapy in many parts of the world (most notably in Eastern Europe and the old Soviet Union), often as a direct replacement for antibiotics.

Phage have been used successfully in several in vivo research studies examining their efficacy on diseases that impact production efficiency or health in swine, sheep and poultry (Huff et al., 2002; Smith and Huggins, 1983, 1982). However, only recently have phages been suggested as a means to control E. coli O157:H7 in food animals (Kudva et al., 1999).

In preliminary studies by our research group, several naturally occurring bacteriophage active against E. coli O157:H7 were isolated from sheep around the U.S. When sheep were transported from open rangeland, 46% of them were found to naturally harbor E. coli O157:H7-killing bacteriophages (Callaway et al., 2003).  Therapeutic trials using a cocktail of bacteriophage inoculated into sheep artificially infected with E. coli O157:H7 reduced concentrations of E. coli O157:H7 throughout the gastrointestinal tract; while these differences were not statistically significant, they were encouraging as a “proof- of–concept” for the use of bacteriophage to control foodborne pathogens in the ruminant gastrointestinal tract (Callaway et al., 2003). The effectiveness of phage treatment under “real world” conditions has been variable in the literature, therefore more basic and applied work needs to be completed before bacteriophage can be considered a viable method to control foodborne pathogenic bacteria in cattle.  The objectives of this study were to isolate and characterize several E. coli O157:H7 infecting bacteriophage from feedlot manure and test their efficacy as a pre-harvest intervention strategy to reduce E. coli O157:H7 in ruminants.

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