{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:56:37Z","timestamp":1772765797582,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2022C03060"],"award-info":[{"award-number":["2022C03060"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,7,31]]},"abstract":"ABSTRACT<\/jats:title>\n \n NAD\n +<\/jats:sup>\n and its derivatives, which act as redox coenzymes, are crucial for cellular metabolism and energy production. Nevertheless, the processes by which\n \n Streptococcus mutans<\/jats:italic>\n <\/jats:styled-content>\n , a bacterium known for causing dental caries, synthesizes NAD\n +<\/jats:sup>\n are not well elucidated. Through a genome\u2010wide screen, we identified the nicotinic acid salvage pathway and the evolutionarily incomplete PnuC\u2013NadR pathway involved in NAD\n +<\/jats:sup>\n biosynthesis in\n \n S.\u2009mutans<\/jats:italic>\n <\/jats:styled-content>\n UA159. The nicotinic acid pathway is regulated by\n Sm<\/jats:italic>\n NiaR, a nicotinic acid\u2010responsive transcription regulator featuring an N\u2010terminal DNA\u2010binding winged helix\u2010turn\u2010helix\u2010like domain and a C\u2010terminal 3\u2010histidine domain. Notably, a single\u2010site amino acid substitution at site K97 in\n Sm<\/jats:italic>\n NiaR can reverse its DNA\u2010binding ability, an effect mediated by acetylation at this site, which impacts the intracellular production of NAD\n +<\/jats:sup>\n and NADH. Additionally, the deletion of\n niaR<\/jats:italic>\n in\n \n S.\u2009mutans<\/jats:italic>\n <\/jats:styled-content>\n UA159 impaired bacterial proliferation, reduced acid production, and altered biofilm formation, resulting in attenuated virulence in the rat caries model. Conclusively, the regulation of NAD\n +<\/jats:sup>\n homeostasis via\n Sm<\/jats:italic>\n NiaR contributes significantly to the cariogenic virulence of\n \n S.\u2009mutans<\/jats:italic>\n <\/jats:styled-content>\n .\n <\/jats:p>","DOI":"10.1096\/fj.202500944r","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T13:40:36Z","timestamp":1753191636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of the Nicotinamide Adenine Dinucleotide Biosynthesis Pathway and Regulatory Mechanisms in\n \n Streptococcus mutans<\/i>\n <\/scp>"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2961-9750","authenticated-orcid":false,"given":"Haojie","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health 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Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province Shulan International Medical College, Zhejiang Shuren University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoxi","family":"Tao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Key Laboratory of Pollution Exposure and Health Intervention of Zhejiang Province Shulan International Medical College, Zhejiang Shuren University Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Sang","sequence":"additional","affiliation":[{"name":"Department of Genetics The University of Texas MD Anderson Cancer Center Houston USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Genetics 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