Since 2001 we have been working on phage that infect Escherichia coli O157:H7. This grant is part of our ongoing work in association with Dr. Betty Kutter and Dr. Todd Callaway.  Here is some of the background on the work.
 
 

Bacteriophage: A bacteriophage in simple terms is a virus that infects bacteria. As with most viruses the phage is highly specific in what it specific phage will only infect a specific host bacterium. Using a phage for our work has a number of distinct advantages. Bacteriophage Lab Homepage

Since the advent of antibiotics in the 1940’s, both the health care and agriculture sectors have relied heavily on chemotherapy to control pathogens. However, increasing numbers of antibiotic resistant bacteria have reduced the efficacy of many current therapies. Further, new drug discovery has not kept pace with the spread of resistance or the rate of bacterial resistance development. This has led researchers to seek fresh ideas that incorporate old and new technologies to combat the problem. Phage therapy is one such “old” idea undergoing a renaissance. Developed early in the 20th century, its initial effectiveness was controversial. However, increased scientific knowledge about phage has highlighted their long overlooked potential for resolving the antibiotic resistant bacterial predicament we find ourselves in today.

Escherichia coli O157:H7 is an important food-borne pathogen, causing severe diarrhea, kidney damage and death. In the U.S. alone, >70,000 illnesses, 2000 hospitalisations, and 60 deaths have been reported yearly (Mead et al. 1998, USDA:ERS 2001). Outbreaks have been linked to the consumption of hamburger meat, alfalfa sprouts, fruit juice, and even drinking water however most cases (>75%) can be traced to exposure to ruminants (Elder et al., 2001; Mead et al., 1998, USDA:APHIS 1997). The most recent data has suggested that 28% of U.S. cattle presented for slaughter harbour O157:H7 (Elder et al., 2000). Reducing the population of O157:H7 in ruminant intestines could therefore significantly reduce the incidence of human infection.
 

Phage CEV1 as isolated from Sheep

CEV1 plaques on E. coli O157:H7 ATCC 700728

CEV1 is a T-even Phage

The discontinuation of antibiotic use as a feed additive in livestock is approaching reality because of the increasing numbers of antibiotic resistant bacteria. Current pre-harvest intervention strategies include pre-biotic feed-grade antimicrobials, and ionophores i.e. rumensin (Elder et al., 2002, Edrington et al., 2003). Using phage therapy as a complementary intervention method might add an important new weapon to this declining arsenal.

Our work has focused on removing O157:H7 from the food chain. CEV1 maybe a promising new way of reducing pathogen concentrations in livestock prior to slaughter via a natural, non-antibiotic approach. This takes advantage of bacteriophages – bacteria-killing viruses that are harmless to humans and other animals and have been used extensively as antibiotics in Eastern Europe and the former Soviet Union for over 50 years. CEV1 was  isolated from the feces of sheep naturally resistant to gut colonization by O157:H7 strains. Preliminary trials of CEV1 in the lab have been highly successful; in model systems reflecting the cow/sheep gut, CEV1 completely eliminated the two tested 0157:H7 strains in 11 days. Initial animal studies have shown that CEV1 has great promise as an orally administered treatment for the selective removal of O157:H7 from farm livestock. We hope with further development this may be a significant breakthrough in the important job of creating a safer human food supply for the 21st Century.

This work was spearheaded by the Phage Lab at The Evergreen State College, Olympia, WA (TESC), where studies of phage molecular biology, physiology and ecology have been carried out for 30 years as part of the academic program. Bacteriophage CEV1 was originally isolated and studied by Peter Varey, an Evergreen undergraduate interning with USDA scientists Todd Callaway and Tom Edrington at College Station, TX. Characterization of CEV1 was carried out at TESC by undergraduate Mike Dyen aided by Gautum Dutta and other students. Chemostat and animal studies were carried out at the USDA by Evergreen Sabbatical Fellow Raul Raya, from Tucuman, Argentina, in conjunction with Dr Callaway. The project was managed and directed by faculty members Andrew D. Brabban and Elizabeth Kutter.

Thursday February 28, 2008 2:06 PM