Warnick

Sources and transmission of multidrug-resistant Salmonella strains that cause human infection

Non-typhoidal salmonellosis is a zoonotic disease and is currently the second most frequent cause of bacterial food-borne illness in the United States (26). Increasing proportions of multi-drug resistance in non-typhoidal Salmonella enterica has increased the risk of treatment failure in severely affected individuals, particularly pediatric cases. FWD-IRN projects at both the Cornell University ZRU and the Washington State University ZRU have demonstrated that a large number of human infections with MDR Salmonella are caused by specific S. Newport and S. Typhimurium strains (identified using pulsed-field gel electrophoresis, PFGE, or multilocus sequence typing, MLST) that are also among the most common MDR Salmonella found in dairy cattle. Here we propose a specific study to further elucidate the sources and transmission of MDR Salmonella, using molecular epidemiologic procedures with the ability to identify strain sub-types within these MDR Salmonella epidemic groups. The hypothesis of our research is that cattle are a reservoir for human infections with these MDR strains and that specific control strategies can be designed to reduce infection with these pathogens. Aim 1 will involve validation and use of multiple-locus variable number of tandem repeat analysis (MLVA) as a subtyping tool with potentially greater discriminatory power than either pulsed-field gel electrophoresis (PFGE) or multi-locus sequence typing. Aim 2 will involve retrospective comparisons of isolates from different species, geographic regions, and time periods. Patterns of genetic change over time and geographic distance will be examined with a focus on accumulation or loss of resistance genes. Aim 3 will continue the prospective comparisons between human and animal Salmonella isolates using multiple molecular methods and with a focus on MDR isolates. Aim 4. will utilize a case-control study design to identify risk factors for acquiring MDR-Salmonella infections. Aim 5. will generate and test hypotheses regarding effective control strategies. Because of the known regional differences in relative prevalence of Salmonella epidemic strain types in animal and human populations, this joint research project at the two Zoonoses Research Units will greatly enhance the power of the epidemiologic analyses, and will significantly strengthen our diagnostic and molecular epidemiologic capabilities to effectively respond to naturally occurring outbreaks or potential bioterrorism incidents involving MDR Salmonella.