CHARACTERIZATION, DISTRIBUTION, AND EVOLUTIONARY ACQUISITION OF ANTIMICROBIAL RESISTANCE ELEMENTS AMONG DIVERSE SALMONELLA SUBSPECIES

Abstract

Insights into the evolution of antimicrobial resistance can be gleaned by examination of historical strains of Salmonella collected from a variety of locations, time periods, and sources. Here, the Salmonella Reference Collections were utilized to gain evidence into the distribution, prevalence, and reticulate nature of antimicrobial resistance from strains that represent the collective genetic diversity of Salmonella. Of the 141 strains examined, 25.5% were fully or intermediately resistant to one or more agents. Resistance to the older antimicrobials sulfisoxazole and streptomycin were more common than resistance to newer antimicrobials, with 15.6% and 14.2% of strains resistant, respectively. No strains presented with resistance to newer drugs--ciprofloxacin, cefoxitin, and ceftiofur specifically. Of particular importance was the identification of a correlation between strains isolated from food animal sources and the presence of resistance to streptomycin and kanamycin, as food animals have been implicated in the transfer of resistance elements through the food chain. Increased incidences of resistance were identified in serotypes Saintpaul, Heidelberg, and Typhimurium. Integrons, a major contributor to the horizontal transfer of resistance genes, were identified in 9.93% of strains and the most commonly harbored gene was aadA1, conferring resistance to streptomycin. Identification of exogenous genes responsible for the observed phenotypes revealed that 73.1% of resistant phenotypes could be accounted for by the presence of such an element. Analysis of horizontal gene transfer among the regulatory mar, ram and sox operon regions, which have been implicated in the development of multi-drug resistance via increased cellular efflux, revealed that recombination helped to maintain a handful of presumably beneficial alleles across subspecies I S. enterica. Diversification was particularly limited in the sox operon and in the global regulatory genes, as opposed to local regulators. Such lack of diversity speaks to the requirement for proper functioning of many processes in the cell. Retention of some clonality was seen in the closely-related SARA strains, with assortment of alleles more obvious across the more diverse SARB strains. Supported by evidence gathered here is the importance of horizontal gene transfer in evolution of selective benefits harbored by bacterial pathogens, in particular, S. enterica.