{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:23:53Z","timestamp":1788269033027,"version":"build-2803163510"},"reference-count":81,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI125421, R01 AI127793, U19 AI144182"],"award-info":[{"award-number":["R01 AI125421, R01 AI127793, U19 AI144182"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Neisseria gonorrhoeae<\/jats:italic>\n , an obligate human pathogen, causes the sexually transmitted infection gonorrhea. Delayed treatment or immunodeficiencies can result in a higher risk of disseminated gonococcal infection (DGI), where the infection spreads to normally sterile anatomic sites, including the bloodstream. The gonococcus produces TonB-dependent transporters (TdTs) to sequester metals from host nutritional immunity proteins. These transporters are critical for survival and are important virulence factors. We characterized genes encoding iron-regulated TdTs in the genomes of strains from disseminated (\n n<\/jats:italic>\n = 47), urogenital (\n n<\/jats:italic>\n = 86), and rectal (\n n<\/jats:italic>\n = 12) infections. We found that gonococcal strains isolated from DGI infections were more likely to express a functional hemoglobin-iron utilization operon (\n hpuAB<\/jats:italic>\n wild type and phase on [32%,\n n<\/jats:italic>\n = 15\/47]), to harbor nonsense mutations in\n tdfF<\/jats:italic>\n (57%,\n n<\/jats:italic>\n = 27\/47), and were predicted to express low levels of\n fetA<\/jats:italic>\n (43%,\n n<\/jats:italic>\n = 20\/47) when compared to strains from urogenital or rectal infections. In contrast, gonococcal strains from localized urogenital infections were associated with a higher frequency of functional\n tdfF<\/jats:italic>\n genes (66%,\n n<\/jats:italic>\n = 57\/86) and high\n fetA<\/jats:italic>\n expression (30%,\n n<\/jats:italic>\n = 26\/86). Additionally, strains from rectal infections were more frequently found to have high\n fetA<\/jats:italic>\n expression (33%,\n n<\/jats:italic>\n = 4\/12) and a functional\n tdfF<\/jats:italic>\n (75%,\n n<\/jats:italic>\n = 9\/12). Furthermore, we identified associations between the presence and absence of\n tdfF<\/jats:italic>\n and the gonococcal genetic island, which encodes a type IV secretion system. These findings inform our evolving understanding of the molecular mechanisms underlying disseminated gonococcal infections.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n Gonorrhea is an emerging, global health threat, with over 100 million new cases each year. Delayed treatment, immunosuppressive medications, and immunodeficiencies can contribute to the spread of infection to the blood, presenting as a serious disseminated manifestation. With rising antimicrobial resistance and no licensed preventative vaccine, untreatable gonorrhea is a possibility in the near future. TonB-dependent transporters are highly conserved and vital for metal acquisition and survival, making them promising targets for therapeutic or preventative strategies. Associated surface-exposed lipoproteins display greater sequence variation but contribute to metal acquisition. We analyzed the genes encoding TonB-dependent transporters and associated lipoproteins from strains associated with distinct disease manifestations. We conclude that gonococci isolated from disseminated, urogenital, and rectal sites demonstrate different phase and allelic variations in genes encoding iron transport systems and the gonococcal genetic island.<\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.01338-26","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:01:11Z","timestamp":1786366871000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Genomic analysis of\n Neisseria gonorrhoeae<\/i>\n strains from disseminated, urogenital, and rectal infections reveals differences in genes for iron acquisition and type IV secretion"],"prefix":"10.1128","volume":"14","author":[{"given":"Natalie S.","family":"Nunnally","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Biomedical Sciences, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7269-1133","authenticated-orcid":true,"given":"Julie L.","family":"Stoudenmire","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Biomedical Sciences, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-0295","authenticated-orcid":true,"given":"Odile B.","family":"Harrison","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Nuffield Department of Population Health, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Unitt","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"Nuffield Department of Population Health, University of Oxford","place":["Oxford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-0324","authenticated-orcid":true,"given":"Ellen N.","family":"Kersh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04wcf8366","id-type":"ROR","asserted-by":"publisher"}],"name":"Georgia Public Health Laboratory, Georgia Department of Public Health","place":["Decatur, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6294-6588","authenticated-orcid":true,"given":"Cynthia Nau","family":"Cornelissen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03qt6ba18","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Biomedical Sciences, Georgia State University","place":["Atlanta, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","unstructured":"WHO. 2021. 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Available from: https:\/\/www.gsk.com\/en-gb\/media\/press-releases\/blujepa-gepotidacin-approved-by-us-fda-as-oral-option-for-treatment-of-uncomplicated-urogenital-gonorrhoea-ugc. Retrieved 1 May 2025."},{"key":"e_1_3_5_6_2","unstructured":"Therapeutics I.S. 2025. U.S. FDA approves NUZOLVENCE (zoliflodacin) a first-in-class single-dose oral antibiotic for the treatment of uncomplicated urogenital gonorrhea in adults and adolescents. Available from: https:\/\/innovivaspecialtytherapeutics.com\/u-s-fda-approves-nuzolvence-zoliflodacin-a-first-in-class-single-dose-oral-antibiotic-for-the-treatment-of-uncomplicated-urogenital-gonorrhea-in-adults-and-adolescents. Retrieved 12 Dec 2025."},{"key":"e_1_3_5_7_2","unstructured":"Organization W.H. 2023. Multi-drug resistant gonorrhoea"},{"key":"e_1_3_5_8_2","unstructured":"Health D.o.P. 2023. 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In Holmes KK, Stamm WE, Piot P, Wasserheit JN, Corey L, Cohen MS, Watts DH (ed), Sexually transmitted diseases. McGraw-Hill, New York."},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-102-2-229"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.4.965-981.2004"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31825a6bc9"},{"key":"e_1_3_5_20_2","unstructured":"Division of STD Prevention National Center for HIV Viral Hepatitis STD and TB Prevention Centers for Disease Control and Prevention. 2021. 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