{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:20:05Z","timestamp":1791519605321,"version":"4.3.4"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,12,4]],"date-time":"2012-12-04T00:00:00Z","timestamp":1354579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2012,12,31]],"date-time":"2012-12-31T00:00:00Z","timestamp":1356912000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2012,12,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            MtrA is a member of the AraC family of transcriptional regulators and has been shown to play an important role in enhancing transcription of the\n            <jats:italic>mtrCDE<\/jats:italic>\n            operon, which encodes a tripartite multidrug efflux pump, when gonococci are exposed to a sublethal level of antimicrobials. Heretofore, the DNA-binding properties of MtrA were unknown. In order to understand how MtrA activates\n            <jats:italic>mtrCDE<\/jats:italic>\n            expression, we successfully purified MtrA and found that it could bind specifically to the\n            <jats:italic>mtrCDE<\/jats:italic>\n            promoter region. The affinity of MtrA for the\n            <jats:italic>mtrCDE<\/jats:italic>\n            promoter increased 2-fold in the presence of a known effector and substrate of the MtrCDE pump, the nonionic detergent Triton X-100 (TX-100). When placed in competition with MtrR, the transcriptional repressor of\n            <jats:italic>mtrCDE<\/jats:italic>\n            , MtrA was found to bind with apparent lower affinity than MtrR to the same region. However, preincubation of MtrA with TX-100 prior to addition of the promoter-containing DNA probe increased MtrA binding and greatly reduced its dissociation from the promoter upon addition of MtrR. Two independent approaches (DNase I footprinting and a screen for bases important in MtrA binding) defined the MtrA-binding site 20\u201330\u00a0bp upstream of the known MtrR-binding site. Collectively, these results suggest that the MtrA and MtrR-binding sites are sterically close and that addition of an effector increases the affinity of MtrA for the\n            <jats:italic>mtrCDE<\/jats:italic>\n            promoter such that MtrR binding is negatively impacted. Our results provide a mechanism for transcriptional activation of\n            <jats:italic>mtrCDE<\/jats:italic>\n            by MtrA and highlight the complexity of transcriptional control of drug efflux systems possessed by gonococci.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Antibiotic resistance in\n            <jats:named-content content-type=\"genus-species\">Neisseria gonorrhoeae<\/jats:named-content>\n            has been increasing in recent years, such that in 2007 the Centers for Disease Control and Prevention listed\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            as a \u201csuperbug.\u201d One of the major contributors to antibiotic resistance in\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            is the MtrCDE efflux pump. Until now, most work on the regulation of the genes encoding this efflux pump has been done on the transcriptional repressor, MtrR. This study is the first one to purify and define the DNA-binding ability of the transcriptional activator, MtrA. Understanding how levels of the MtrCDE efflux pump are regulated increases our knowledge of gonococcal biology and how the gonococcus can respond to various stresses, including antimicrobials.\n          <\/jats:p>","DOI":"10.1128\/mbio.00446-12","type":"journal-article","created":{"date-parts":[[2012,12,6]],"date-time":"2012-12-06T01:38:08Z","timestamp":1354757888000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Dueling Regulatory Properties of a Transcriptional Activator (MtrA) and Repressor (MtrR) That Control Efflux Pump Gene Expression in Neisseria gonorrhoeae"],"prefix":"10.1128","volume":"3","author":[{"given":"Yaramah M.","family":"Zalucki","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya","family":"Dhulipala","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"},{"name":"Laboratories of Bacterial Pathogenesis, VA Medical Center, Decatur, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-148-8-200804150-00005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.4.1829"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-141-3-611"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.10.5576-5582.2003"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.13.4123-4128.1997"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.14.4162-4165.1995"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01517.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.14.5008-5012.2005"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.20.5619-5624.2002"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","unstructured":"OhneckEA\n. 2011. 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