QacR is a repressor protein that regulates expression of the Staphylococcus aureus multidrug efflux pump QacA - PubMed (original) (raw)
. 1998 Jul 17;273(29):18665-73.
doi: 10.1074/jbc.273.29.18665.
Affiliations
- PMID: 9660841
- DOI: 10.1074/jbc.273.29.18665
Free article
QacR is a repressor protein that regulates expression of the Staphylococcus aureus multidrug efflux pump QacA
S Grkovic et al. J Biol Chem. 1998.
Free article
Abstract
The Staphylococcus aureus QacA protein is a multidrug transporter that confers resistance to a broad range of antimicrobial agents via proton motive force-dependent efflux of the compounds. Primer extension analysis was performed to map the transcription start points of the qacA and divergently transcribed qacR mRNAs. Each gene utilized a single promoter element, the locations of which were confirmed by site-directed mutagenesis. Fusions of the qacA and qacR promoters to a chloramphenicol acetyl transferase reporter gene were used to demonstrate that QacR is a trans-acting repressor of qacA transcription that does not autoregulate its own expression. An inverted repeat overlapping the qacA transcription start site was shown to be the operator sequence for control of qacA gene expression. Removal of one half of the operator prevented QacR-mediated repression of the qacA promoter. Purified QacR protein bound specifically to this operator sequence in DNase I-footprinting experiments. Importantly, addition of diverse QacA substrates was shown to induce qacA expression in vivo, as well as inhibit binding of QacR to operator DNA in vitro, by using gel-mobility shift assays. QacR therefore appears to interact directly with structurally dissimilar inducing compounds that are substrates of the QacA multidrug efflux pump.
Similar articles
- Staphylococcal multidrug efflux protein QacA.
Brown MH, Skurray RA. Brown MH, et al. J Mol Microbiol Biotechnol. 2001 Apr;3(2):163-70. J Mol Microbiol Biotechnol. 2001. PMID: 11321569 Review. - The staphylococcal QacR multidrug regulator binds a correctly spaced operator as a pair of dimers.
Grkovic S, Brown MH, Schumacher MA, Brennan RG, Skurray RA. Grkovic S, et al. J Bacteriol. 2001 Dec;183(24):7102-9. doi: 10.1128/JB.183.24.7102-7109.2001. J Bacteriol. 2001. PMID: 11717268 Free PMC article. - Interactions of the QacR multidrug-binding protein with structurally diverse ligands: implications for the evolution of the binding pocket.
Grkovic S, Hardie KM, Brown MH, Skurray RA. Grkovic S, et al. Biochemistry. 2003 Dec 30;42(51):15226-36. doi: 10.1021/bi035447+. Biochemistry. 2003. PMID: 14690433 - Structural basis for cooperative DNA binding by two dimers of the multidrug-binding protein QacR.
Schumacher MA, Miller MC, Grkovic S, Brown MH, Skurray RA, Brennan RG. Schumacher MA, et al. EMBO J. 2002 Mar 1;21(5):1210-8. doi: 10.1093/emboj/21.5.1210. EMBO J. 2002. PMID: 11867549 Free PMC article. - Deciphering the molecular basis of multidrug recognition: crystal structures of the Staphylococcus aureus multidrug binding transcription regulator QacR.
Schumacher MA, Brennan RG. Schumacher MA, et al. Res Microbiol. 2003 Mar;154(2):69-77. doi: 10.1016/S0923-2508(02)00013-X. Res Microbiol. 2003. PMID: 12648720 Review.
Cited by
- A copper-responsive global repressor regulates expression of diverse membrane-associated transporters and bacterial drug resistance in mycobacteria.
Rao M, Liu H, Yang M, Zhao C, He ZG. Rao M, et al. J Biol Chem. 2012 Nov 16;287(47):39721-31. doi: 10.1074/jbc.M112.383604. Epub 2012 Sep 25. J Biol Chem. 2012. PMID: 23014988 Free PMC article. - The mobilome landscape of biocide-resistance in Brazilian ESKAPE isolates.
da Rosa EEB, Kremer FS. da Rosa EEB, et al. Braz J Microbiol. 2024 Dec;55(4):3603-3616. doi: 10.1007/s42770-024-01450-7. Epub 2024 Jul 19. Braz J Microbiol. 2024. PMID: 39028534 - Targeting the Holy Triangle of Quorum Sensing, Biofilm Formation, and Antibiotic Resistance in Pathogenic Bacteria.
Sionov RV, Steinberg D. Sionov RV, et al. Microorganisms. 2022 Jun 16;10(6):1239. doi: 10.3390/microorganisms10061239. Microorganisms. 2022. PMID: 35744757 Free PMC article. Review. - Regulation of transcription by SMU.1349, a TetR family regulator, in Streptococcus mutans.
Chattoraj P, Mohapatra SS, Rao JL, Biswas I. Chattoraj P, et al. J Bacteriol. 2011 Dec;193(23):6605-13. doi: 10.1128/JB.06122-11. Epub 2011 Sep 30. J Bacteriol. 2011. PMID: 21965566 Free PMC article. - Characterization of BreR interaction with the bile response promoters breAB and breR in Vibrio cholerae.
Cerda-Maira FA, Kovacikova G, Jude BA, Skorupski K, Taylor RK. Cerda-Maira FA, et al. J Bacteriol. 2013 Jan;195(2):307-17. doi: 10.1128/JB.02008-12. Epub 2012 Nov 9. J Bacteriol. 2013. PMID: 23144245 Free PMC article.