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

Buckner, MMC, Blair, JM, La Ragione, RM, Newcombe, J, Dwyer, DJ, Ivens, A and Piddock, LJV (2016) Beyond Antimicrobial Resistance: Evidence for a Distinct Role of the AcrD Efflux Pump in Salmonella Biology mBio, 7 (6).

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Abstract

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.

Item Type: Article
Subjects : Veterinary Medicine
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
AuthorsEmailORCID
Buckner, MMCUNSPECIFIEDUNSPECIFIED
Blair, JMUNSPECIFIEDUNSPECIFIED
La Ragione, RMUNSPECIFIEDUNSPECIFIED
Newcombe, JUNSPECIFIEDUNSPECIFIED
Dwyer, DJUNSPECIFIEDUNSPECIFIED
Ivens, AUNSPECIFIEDUNSPECIFIED
Piddock, LJVUNSPECIFIEDUNSPECIFIED
Date : 22 November 2016
Identification Number : https://doi.org/10.1128/mBio.01916-16
Copyright Disclaimer : Copyright © 2016 Buckner et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Depositing User : Symplectic Elements
Date Deposited : 19 Dec 2016 13:03
Last Modified : 19 Dec 2016 13:03
URI: http://epubs.surrey.ac.uk/id/eprint/813143

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