{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:37:57Z","timestamp":1785307077187,"version":"3.55.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2011,9,20]],"date-time":"2011-09-20T00:00:00Z","timestamp":1316476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2011,11,1]],"date-time":"2011-11-01T00:00:00Z","timestamp":1320105600000},"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":[[2011,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The MtrC-MtrD-MtrE multidrug efflux pump of\n            <jats:named-content content-type=\"genus-species\">Neisseria gonorrhoeae<\/jats:named-content>\n            confers resistance to a diverse array of antimicrobial agents by transporting these toxic compounds out of the gonococcus. Frequently in gonococcal strains, the expression of the\n            <jats:italic>mtrCDE<\/jats:italic>\n            operon is differentially regulated by both a repressor, MtrR, and an activator, MtrA. The\n            <jats:italic>mtrR<\/jats:italic>\n            gene lies 250\u00a0bp upstream of and is transcribed divergently from the\n            <jats:italic>mtrCDE<\/jats:italic>\n            operon. Previous research has shown that mutations in the\n            <jats:italic>mtrR<\/jats:italic>\n            coding region and in the\n            <jats:italic>mtrR<\/jats:italic>\n            -\n            <jats:italic>mtrCDE<\/jats:italic>\n            intergenic region increase levels of gonococcal antibiotic resistance and\n            <jats:italic>in vivo<\/jats:italic>\n            fitness. Recently, a C-to-T transition mutation 120\u00a0bp upstream of the\n            <jats:italic>mtrC<\/jats:italic>\n            start codon, termed\n            <jats:italic>mtr<\/jats:italic>\n            <jats:sub>120<\/jats:sub>\n            , was identified in strain MS11 and shown to be sufficient to confer high levels of antimicrobial resistance when introduced into strain FA19. Here we report that this mutation results in a consensus \u221210 element and that its presence generates a novel promoter for\n            <jats:italic>mtrCDE<\/jats:italic>\n            transcription. This newly generated promoter was found to be stronger than the wild-type promoter and does not appear to be subject to MtrR repression or MtrA activation. Although rare, the\n            <jats:italic>mtr<\/jats:italic>\n            <jats:sub>120<\/jats:sub>\n            mutation was identified in an additional clinical isolate during sequence analysis of antibiotic-resistant strains cultured from patients with gonococcal infections. We propose that\n            <jats:italic>cis<\/jats:italic>\n            -acting mutations can develop in gonococci that significantly alter the regulation of the\n            <jats:italic>mtrCDE<\/jats:italic>\n            operon and result in increased resistance to antimicrobials.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Gonorrhea is the second most prevalent sexually transmitted bacterial infection and a worldwide public health concern. As there is currently no vaccine against\n            <jats:named-content content-type=\"genus-species\">Neisseria gonorrhoeae<\/jats:named-content>\n            , appropriate diagnostics and subsequent antibiotic therapy remain the primary means of infection control. However, the effectiveness of antibiotic treatment is constantly challenged by the emergence of resistant strains, mandating a thorough understanding of resistance mechanisms to aid in the development of new antimicrobial therapies and genetic methods for antimicrobial resistance testing. This study was undertaken to characterize a novel mechanism of antibiotic resistance regulation in\n            <jats:named-content content-type=\"genus-species\">N. gonorrhoeae<\/jats:named-content>\n            . Here we show that a single base pair mutation generates a second, stronger promoter for\n            <jats:italic>mtrCDE<\/jats:italic>\n            transcription that acts independently of the known efflux system regulators and results in high-level antimicrobial resistance.\n          <\/jats:p>","DOI":"10.1128\/mbio.00187-11","type":"journal-article","created":{"date-parts":[[2011,9,21]],"date-time":"2011-09-21T03:09:09Z","timestamp":1316574549000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["A Novel Mechanism of High-Level, Broad-Spectrum Antibiotic Resistance Caused by a Single Base Pair Change in Neisseria gonorrhoeae"],"prefix":"10.1128","volume":"2","author":[{"given":"Elizabeth A.","family":"Ohneck","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaramah M.","family":"Zalucki","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J. 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