Abstract
Salmonella enterica serovar Typhimurium has at least nine multidrug efflux pumps. Among these pumps, AcrAB is effective in generating drug resistance and has wide substrate specificity. Here we report that indole, bile, and an Escherichia coli conditioned medium induced the AcrAB pump in Salmonella through a specific regulator, RamA. The RamA-binding sites were located in the upstream regions of acrAB and tolC. RamA was required for indole induction of acrAB. Other regulators of acrAB such as MarA, SoxS, Rob, SdiA, and AcrR did not contribute to acrAB induction by indole in Salmonella. Indole activated ramA transcription, and overproduction of RamA caused increased acrAB expression. In contrast, induction of ramA was not required for induction of acrAB by bile. Cholic acid binds to RamA, and we suggest that bile acts by altering pre-existing RamA. This points to two different AcrAB regulatory modes through RamA. Our results suggest that RamA controls the Salmonella AcrAB-TolC multidrug efflux system through dual regulatory modes in response to environmental signals.
Highlights
Salmonella enterica is a bacterial pathogen that causes a variety of diseases in humans, including gastroenteritis, bacteremia, and typhoid fever [1]
Ance in S. enterica serovar Typhimurium phage type DT204 has been reported to result from multiple target gene mutations and active efflux by the AcrAB-TolC multidrug efflux pump [13, 14]
Indole Induces Four Multidrug Efflux Pumps and Drug Tolerance of Salmonella—In E. coli, indole is produced from tryptophan by tryptophanase and is excreted from the cell [42]
Summary
Strains as in text WT tolC-lac acrAB-lac acrEF-lac acrD-lac mdtABC-lac mdsABC-lac emrAB-lac mdfA-lac mdtK-lac macAB-lac ⌬baeSR cpxAR/acrAB-lac ⌬baeSR cpxAR/acrD-lac ⌬marA/acrAB-lac ⌬soxS/acrAB-lac ⌬rob/acrAB-lac ⌬sdiA/acrAB-lac ⌬acrR/acrAB-lac ⌬marA rob soxS sdiA acrR/acrAB-lac ⌬ramA/acrAB-lac ⌬ramA/tolC-lac. S. enterica serovar Typhimurium wild-type ⌬tolC-lacZYϩ KmR ⌬acrAB-lacZYϩ KmR ⌬acrEF-lacZYϩ KmR ⌬acrD-lacZYϩ KmR ⌬mdtABC-lacZYϩ KmR ⌬mdsABC-lacZYϩ KmR ⌬emrAB-lacZYϩ KmR ⌬mdfA-lacZYϩ KmR ⌬mdtK-lacZYϩ KmR ⌬macAB-lacZYϩ KmR ⌬baeSR ⌬cpxAR::CmR ⌬acrAB-lacZYϩ KmR ⌬baeSR ⌬cpxAR::CmR ⌬acrD-lacZYϩ KmR ⌬marA::CmR ⌬acrAB-lacZYϩ KmR ⌬soxS::CmR ⌬acrAB-lacZYϩ KmR ⌬rob::CmR ⌬acrAB-lacZYϩ KmR ⌬sdiA::CmR ⌬acrAB-lacZYϩ KmR ⌬acrR::CmR ⌬acrAB-lacZYϩ KmR ⌬marA ⌬rob ⌬soxS ⌬sdiA ⌬acrR::CmR ⌬acrAB-lacZYϩ KmR ⌬ramA::CmR ⌬acrAB-lacZYϩ KmR ⌬ramA::CmR ⌬tolC-lacZYϩ KmR repR6KgrApRFRT CmRFRT repR6KgrApRFRT KmRFRT reppSC101ts ApR CmR cI857lPRflp Vector, AmpR ramA-His gene cloned into pMALc2X, AmpR 5Ј-Terminal (69 bp) deleted ramA-His gene cloned into pMALc2X, AmpR Single copy vector, CmR, NotI-HindIII cloning site upstream of promoter-less lacZ pNN387 (ramA gene promoter-lacZ). This study pump genes in E. coli [35] They reported that indole induction of acrD and mdtA is mediated by the BaeSR and CpxAR systems. We report on induction of acrAB in Salmonella via the specific regulator RamA in response to indole, bile, and an E. coli conditioned medium. This study describes the dual regulatory mode of acrAB via RamA in response to environmental signals
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
