{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:18:20Z","timestamp":1785161900976,"version":"3.55.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["DE19452"],"award-info":[{"award-number":["DE19452"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The <jats:italic>sufCDSUB<\/jats:italic> gene cluster, encoding the sole iron-sulfur (Fe-S) cluster assembly system in <jats:italic>S. mutans<\/jats:italic>, was recently shown to be up-regulated in response to oxidative stressors and Fe limitation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, luciferase reporter fusion assays, electrophoretic gel mobility shift assays (EMSA) and <jats:italic>in vitro<\/jats:italic> transcription assays (IVT) were used to dissect the <jats:italic>cis-<\/jats:italic> and <jats:italic>trans-<\/jats:italic>acting factors that regulate the expression of <jats:italic>sufCDSUB<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>Results showed deletion of <jats:italic>perR<\/jats:italic>, for the only Fur-family transcriptional regulator in <jats:italic>S. mutans<\/jats:italic>, resulted in &amp;gt;5-fold increases in luciferase activity under the control of the <jats:italic>sufCDSUB<\/jats:italic> promoter (P&amp;lt;0.01), as compared to the parent strain, UA159 when the reporter strains were grown in medium with no supplemental iron. Site-directed mutagenesis of a PerR-box in the promoter region led to elevation of the reporter activity by &amp;gt;1.6-fold (<jats:italic>P<\/jats:italic>&amp;lt;0.01). In an EMSA, recombinant PerR (rPerR) was shown to bind to the cognate <jats:italic>sufCDSUB<\/jats:italic> promoter leading to mobility retardation. On the other hand, the reporter activity was increased by &amp;gt;84-fold (P&amp;lt;0.001) in response to the addition of cysteine at 4 mM to the culture medium. Deletion of <jats:italic>cysR<\/jats:italic>, for a LysR-type of transcriptional regulator, led to reduction of the reporter activity by &amp;gt;11.6-fold (<jats:italic>P<\/jats:italic>&amp;lt;0.001). Addition of recombinant CysR (rCysR) to an EMSA caused mobility shift of the <jats:italic>sufCDSUB<\/jats:italic> promoter probe, indicative of rCysR-promoter interaction, and rCysR was shown to enhance <jats:italic>sufC<\/jats:italic> transcription under the direction of <jats:italic>sufCDSUB<\/jats:italic> promoter <jats:italic>in vitro<\/jats:italic>. These results suggest that multiple factors are involved in the regulation of <jats:italic>sufCDSUB<\/jats:italic> expression in response to environmental cues, including cysteine and Fe availability, consistent with the important role of <jats:italic>sufCDSUB<\/jats:italic> in <jats:italic>S. mutans<\/jats:italic> physiology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1499476","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T06:34:32Z","timestamp":1732689272000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Multiple factors regulate the expression of sufCDSUB in Streptococcus mutans"],"prefix":"10.3389","volume":"14","author":[{"given":"Kassapa","family":"Ellepola","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Guillot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley","family":"Comeaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica K.","family":"Kajfasz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob P.","family":"Bitoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Spatafora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Lemos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zezhang T.","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1099\/mic.0.063032-0","article-title":"Psr is involved in regulation of glucan production, and double deficiency of BrpA and Psr is lethal in Streptococcus mutans","volume":"159","author":"Bitoun","year":"2013","journal-title":"Microbiol. 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