{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T01:27:53Z","timestamp":1780450073622,"version":"3.54.1"},"reference-count":46,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01 AI147609"],"award-info":[{"award-number":["R01 AI147609"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI125421, R01 AI127793, U19 AI144182"],"award-info":[{"award-number":["R01AI125421, R01 AI127793, U19 AI144182"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Increasing antibiotic resistance of\n            <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n            , the causative agent of gonorrhea, is a growing global concern that has renewed vaccine development efforts. The gonococcal OmpA protein was previously identified as a vaccine candidate due to its surface exposure, conservation, stable expression, and involvement in host\u2013cell interactions. We previously demonstrated that the transcription of\n            <jats:italic>ompA<\/jats:italic>\n            can be activated by the MisR\/MisS two-component system. Interestingly, earlier work suggested that the availability of free iron also influences\n            <jats:italic>ompA<\/jats:italic>\n            expression, which we confirmed in this study. In the present study, we found that iron regulation of\n            <jats:italic>ompA<\/jats:italic>\n            was independent of MisR and searched for additional regulators. A DNA pull-down assay with the\n            <jats:italic>ompA<\/jats:italic>\n            promoter from gonococcal lysates obtained from bacteria grown in the presence or absence of iron identified an XRE (Xenobiotic Response Element) family member protein encoded by\n            <jats:italic>NGO1982<\/jats:italic>\n            . We found that an\n            <jats:italic>NGO1982<\/jats:italic>\n            null mutant of\n            <jats:italic>N. gonorrhoeae<\/jats:italic>\n            strain FA19 displayed a reduced level of\n            <jats:italic>ompA<\/jats:italic>\n            expression compared to the wild-type (WT) parent strain. Given this regulation, and the capacity of this XRE-like protein to regulate a gene involved in peptidoglycan biosynthesis (\n            <jats:italic>ltgA<\/jats:italic>\n            ), along with its presence in other\n            <jats:italic>Neisseria<\/jats:italic>\n            sp., we termed the\n            <jats:italic>NGO1982-<\/jats:italic>\n            encoded protein as NceR (\n            <jats:italic>\n              <jats:underline>N<\/jats:underline>\n              eisseria\n            <\/jats:italic>\n            <jats:underline>c<\/jats:underline>\n            ell\n            <jats:underline>e<\/jats:underline>\n            nvelope\n            <jats:underline>r<\/jats:underline>\n            egulator). Critically, results from DNA-binding studies indicated that NceR regulates\n            <jats:italic>ompA<\/jats:italic>\n            through a direct mechanism. Thus,\n            <jats:italic>ompA<\/jats:italic>\n            expression is subject to both iron-dependent (NceR) and -independent (MisR\/MisS) pathways. Hence, levels of the vaccine antigen candidate OmpA in circulating gonococcal strains could be influenced by transcriptional regulatory systems and the availability of iron.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Herein, we report that the gene encoding a conserved gonococcal surface-exposed vaccine candidate (OmpA) is activated by a heretofore undescribed XRE family transcription factor, which we term NceR. We report that NceR regulation of\n              <jats:italic>ompA<\/jats:italic>\n              expression in\n              <jats:italic>N. gonorrhoeae<\/jats:italic>\n              is mediated by an iron-dependent mechanism, while the previously described MisR regulatory system is iron-independent. Our study highlights the importance of defining the complexity of coordinated genetic and physiologic systems that regulate genes encoding vaccine candidates to better understand their availability during infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/mbio.01244-23","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T13:17:53Z","timestamp":1688131073000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptional activation of\n            <i>ompA<\/i>\n            in\n            <i>Neisseria gonorrhoeae<\/i>\n            mediated by the XRE family member protein NceR"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0177-4270","authenticated-orcid":true,"given":"Concerta L.","family":"Holley","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":"Stavaros A.","family":"Maurakis","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley Nicole","family":"Greenawalt","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-9680","authenticated-orcid":true,"given":"Timothy D.","family":"Read","sequence":"additional","affiliation":[{"name":"Department of Medicine (Division of Infectious Diseases), Emory University School of Medicine , Atlanta, Georgia, USA"},{"name":"The Emory Antibiotic Resistance Center, Emory University School of Medicine , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia N.","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University , Atlanta, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-8777","authenticated-orcid":true,"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Emory University School of Medicine , Atlanta, Georgia, USA"},{"name":"Department of Medicine (Division of Infectious Diseases), Emory University School of Medicine , Atlanta, Georgia, USA"},{"name":"Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center , Decatur, Georgia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.15620\/cdc.79370"},{"key":"e_1_3_5_3_2","unstructured":"Centers for Disease Control and Prevention\n. 2019. Sexually transmitted disease surveillance 2019: Gonococcal isolate surveillance project (GISP). U.S. Department of Health and Human Services. Available from: https:\/\/www.cdc.gov\/std\/statistics\/gisp-profiles\/default.htm"},{"key":"e_1_3_5_4_2","volume-title":"Sexually transmitted disease surveillance 2019: Gonococcal isolate surveillance project (GISP) supplement and profiles","author":"Centers for Disease Control and Prevention","year":"2021","unstructured":"Centers for Disease Control and Prevention . 2021. Sexually transmitted disease surveillance 2019: Gonococcal isolate surveillance project (GISP) supplement and profiles. 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Whole genome database [Internet]. Bethesda (MD): National Library of Medicine (US) National Center for Biotechnology Information. Available from: https:\/\/www.ncbi.nlm.nih.gov\/genome\/ ed. 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Identification of the DNA bases of a DNAse I footprint by the use of dye primer sequencing on an automated capillary DNA analysis instrument. 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