Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux Pump in Salmonella Biology.

Efflux pumps in Gram-negative bacteria are studied because of their important contributions to antimicrobial resistance. However, the role of these pumps in bacterial biology has remained surprisingly elusive. Here, we provide evidence that loss of the AcrD efflux pump significantly impacts the physiology of Salmonella enterica serovar Typhimurium. Inactivation of acrD led to changes in the expression of 403 genes involved in fundamental processes, including basic metabolism, virulence, and stress responses. Pathways such as these allow Salmonella to grow, survive in the environment, and cause disease. Indeed, our data show that the acrD mutant is more fit than wild-type Salmonella under standard lab conditions. We hypothesized that inactivation of acrD would alter levels of bacterial metabolites, impacting traits such as swarming motility. We demonstrated this by exogenous addition of the metabolite fumarate, which partially restored the acrD mutant's swarming defect. This work extends our understanding of the role of bacterial efflux pumps.