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To provide a fundamental understanding of the factors that govern the emergence and spread of antimicrobial resistance among enteric bacteria in food-producing animals.
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The broad objectives are to:<ol> <li>determine the impact of antimicrobial use in cattle on the prevalence of drug resistance in enteric bacteria;
<li>Elucidate generic mechanisms that contribute to the acquisition, dissemination, and persistance of antimicrobial resistance in food-borne pathogens;
<li>Develop models to quantitatively measure the frequency of emergence and transfer of antimicrobial resistance in response to antimicrobial treatment. </ol>
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Our proposed research should ultimately lead to the development of intervention strategies to combat the antimicrobial resistance problem.
This research is designed to span the continuum of antimicrobial resistance research: from sampling of field isolates, to characterizing their resistance phenotypes and genotypes, and finally, modeling their behavior in a mixed-culture environment of the GI tract. Our research will focus on resistance in large animals, particularly cattle, drawing on our scientists' experience with the beef and dairy industries. Bacterial isolates collected from fecal samples of dairy and feedlot cattle will be characterized for resistance to selected antimicrobials, including antibiotics used in human and veterinary medicine, and chemical disinfectants. Genes responsible for the observed resistance phenotypes will be mapped to mobile genetic elements such as plasmids and integrons, and the potential genetic linkage between multiple-drug resistance genes and virulence factors will be examined. To understand the fate of resistant bacteria and their resistance genes in a natural setting, one must consider the diverse microbial ecology of the gut and the effects antimicrobials have on all species.
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We propose to develop anaerobic cultures of enteric bacteria maintained in continuous-flow chemostats as models of the gut, studying the effects of antimicrobials on population dynamics, horizontal gene transfer, and the ability of the culture to exclude pathogens. Integrating the knowledge obtained from this work will ultimately lead to the development of intervention strategies to combat the dissemination of antimicrobial resistance among enteric bacteria.