Bacteriophage biology and the control of pathogenic bacteria.
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Since the 1940's, bacterial infections have been successfully controlled in humans and animals with antibiotics. Shortly after the introduction of antibiotics, strains of bacteria that were resistant to these drugs began to emerge. Today, the continued emergence of bacterial strains that are resistant to antibiotics has raised significant concern among the general medical community, some even suggesting we may be about to enter a "post-antibiotic era". Antimicrobial resistance (AMR) in bacteria poses a significant threat to the health of Americans. This problem has become greatly potentiated the fact that the pharmaceutical industry has largely abandoned the development of new antibiotics, leaving the development pipeline dry. There is a clear and present need for new antibiotic agents that are effective against AMR bacteria and that can be used in agricultural, veterinary and medical settings. Bacteriophages (typically called "phages") are viruses that infect bacteria. These viruses are the most abundant form of life on Earth, estimated to number some 1031 to 1032 organisms. Phages are ubiquitous, non-toxic and highly successful predators of bacteria, and are naturally present in soil, fresh water, open oceans, and associated with plants and animals as a part of their normal flora. The emergence of widespread antibiotic resistance in a variety of bacteria has sparked interest in the use of phages as antimicrobials. Phages have been shown to be effective in controlling a wide variety of pathogens in animal models, including Salmonella in poultry and swine, pathogenic E. coli in cattle and sheep, and numerous other pathogenic bacteria including Pseudomonas aeruginosa, Enterococcus faecium, Staphylococcus aureus and Klebsiella pneumoniae. This project aims to develop the use of bacteriophages as therapeutics against common foodborne pathogenic bacteria, initially focussing on Salmonella enterica carriage by beef cattle but also branching out into pathogenic E. coli (STEC, EPEC) and Staphylococcus aureus. Phages will be isolated, caharacterized, and their basic biology studied by a combination of classical genetic and modern high-throughput genomics techniques. Thier potential for controlling pathogenic bacteria in a practical setting will be evaluated. The project's ultimate goals are to increase the safety of the food supply and to develop knowledge and methods for further development of this technology.