Yersinia pestis AcrAB-TolC in antibiotic resistance and virulence

Abstract

The efflux pump AcrAB is important in the antibiotic resistance and virulence of several pathogenic bacteria. We report that deletion of the Yersinia pestis AcrAB-TolC homolog leads to increased susceptibility to diverse substrates, including, though unlike in Escherichia coli, the aminoglycosides. Neither is the Y. pestis pump affected by the efflux pump inhibitor phenylalanine-arginine beta-naphthylamide. In mouse plague models, pump deletion does not have a significant effect on tissue colonization.

Fig 1

Drug susceptibilities of wild-type KIM 1001 pgm and acrAB and tolC deletion mutants. The data are representative of at least 3 experiments for each antibiotic. In all instances, deletion caused major increases in drug susceptibility. a, norfloxacin and ciprofloxacin MICs could not be shown for the tolC and acrAB strains, as the boundary of bacterial growth was below the lowest antibiotic concentration of the Etest strip. Asterisks denote significance as calculated by one-way ANOVA with Tukey's posttest, as follows: *, P value of 0.01 to 0.05; **, P value of 0.001 to 0.01; ***, P value of <0.001. AMP, ampicillin; CHL, chloramphenicol; CIP, ciprofloxacin; DOX, doxycycline; GMC, gentamicin; KAN, kanamycin; NAL, nalidixic acid; NOR, norfloxacin; RIF, rifampin; SMC, streptomycin; TET, tetracycline; TMS, trimethoprim-sulfamethoxazole.

Fig 2

Intranasal (A) and intravenous (B) mouse infections. Each symbol in the graphs shows the results for one mouse. The horizontal bar denotes the median.