We have located links that may give you full text access.
Journal Article
Research Support, Non-U.S. Gov't
Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux Pump in Salmonella Biology.
MBio 2016 November 23
For over 20 years, bacterial multidrug resistance (MDR) efflux pumps have been studied because of their impact on resistance to antimicrobials. However, critical questions remain, including why produce efflux pumps under non-antimicrobial treatment conditions, and why have multiple pumps if their only purpose is antimicrobial efflux? Salmonella spp. possess five efflux pump families, including the resistance-nodulation-division (RND) efflux pumps. Notably, the RND efflux pump AcrD has a unique substrate profile, distinct from other Salmonella efflux pumps. Here we show that inactivation of acrD results in a profoundly altered transcriptome and modulation of pathways integral to Salmonella biology. The most significant transcriptome changes were central metabolism related, with additional changes observed in pathogenicity, environmental sensing, and stress response pathway expression. The extent of tricarboxylic acid cycle and fumarate metabolism expression changes led us to hypothesize that acrD inactivation may result in motility defects due to perturbation of metabolite concentrations, such as fumarate, for which a role in motility has been established. Despite minimal detectable changes in flagellar gene expression, we found that an acrD mutant Salmonella enterica serovar Typhimurium isolate was significantly impaired for swarming motility, which was restored by addition of fumarate. The acrD mutant outcompeted the wild type in fitness experiments. The results of these diverse experiments provide strong evidence that the AcrD efflux pump is not simply a redundant system providing response resilience, but also has distinct physiological functions. Together, these data indicate that the AcrD efflux pump has a significant and previously underappreciated impact on bacterial biology, despite only minor perturbations of antibiotic resistance profiles.
IMPORTANCE: 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.
IMPORTANCE: 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.
Full text links
Related Resources
Trending Papers
Challenges in Septic Shock: From New Hemodynamics to Blood Purification Therapies.Journal of Personalized Medicine 2024 Februrary 4
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection.International Journal of Molecular Sciences 2024 April 4
The 'Ten Commandments' for the 2023 European Society of Cardiology guidelines for the management of endocarditis.European Heart Journal 2024 April 18
A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.Journal of Intensive Care Medicine 2024 April 14
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app