The effect of marA on multiple antimicrobial resistance and pathogenesis of Salmonella Choleraesuis

Robert Jon Tibbetts, Purdue University


The marA gene is a member of the araC/xylS family of transcriptional activators most commonly associated with the regulation of stress response, multiple antimicrobial resistance, and virulence. marA is found within the marCRAB operon that has been shown to be inducible through bacterial exposure to various antimicrobial agents and salicylate. Overexpression of marA results in a multiple antimicrobial resistance (MAR) phenotype. While common among many members of the Enterobacteriaceae, the marCRAB operon was found to be absent from Salmonella enterica subspecies enterica serovar choleraesuis. The purpose of this present study was to determine the presence of marA in S. Choleraesuis and determine its role in the regulation of multiple antimicrobial resistance and pathogenesis. The marA gene was found in S. Choleraesuis and was determined to be genetically similar to E. coli and S. Typhimurium. Overexpression of marA was inducible by exposure to salicylate. Induction of marA resulted in increased expression of AcrAB efflux pump mechanism and an increase in the resistance of the organism to multiple antimicrobial agents. Loss of the marA gene abrogated induction of the MAR phenotype. Therefore, marA in S. Choleraesuis is genetically and functionally similar to previously published data on marA and is responsible for the regulation of multiple antimicrobial resistance. Adherence assays of wild type, marA-disrupted, and marA-complemented S. Choleraesuis to polarized Caco-2 epithelial cells revealed adherence was significantly decreased in a marA-dependent manner (p ≤ 0.001). However, invasion and intracellular survival of S. Choleraesuis was not affected by induction of marA. Bacterial adherence to host epithelial cells is often mediated by fimbriae and/or flagella. Expression of fimbriae in S. Choleraesuis was not affected by the presence or induction of marA. However, the motility of S. Choleraesuis, the presence of flagella on S. Choleraesuis surface, and the amount of flagellin protein isolated from S. Choleraesuis were decreased following induction of marA. In summary, MarA is present in S. Choleraesuis and induction of marA increased multiple antimicrobial resistance of S. Choleraesuis through increased AcrAB efflux. Induction of marA also led to decreased adherence of S. Choleraesuis to Caco-2 cells by decreased bacterial mobility and flagellin production.




Wu, Purdue University.

Subject Area

Microbiology|Veterinary services

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