{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T13:24:11Z","timestamp":1788269051727,"version":"build-2803163510"},"reference-count":43,"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\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE019452"],"award-info":[{"award-number":["DE019452"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010477","name":"UniCredit and Universities Foundation","doi-asserted-by":"publisher","award":["DE019452"],"award-info":[{"award-number":["DE019452"]}],"id":[{"id":"10.13039\/501100010477","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":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      This study used a functional genomics approach to explore the role of a xenobiotic response element (XRE)-type regulator (SMU.405c) in\n                      <jats:italic toggle=\"yes\">Streptococcus mutans<\/jats:italic>\n                      physiology, including the expression of biofilm regulatory protein BrpA. Results showed that deletional mutation of\n                      <jats:italic toggle=\"yes\">xre<\/jats:italic>\n                      significantly reduced the ability of the deficient mutant to grow in the presence of methyl viologen, a commonly used oxidative stressor (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). When challenged in a hydrogen peroxide killing assay, the survival rate of the \u2206\n                      <jats:italic toggle=\"yes\">xre<\/jats:italic>\n                      mutant was &gt;2-log less than the parent strain after 60 min (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). Luciferase reporter fusion assays showed that\n                      <jats:italic toggle=\"yes\">xre<\/jats:italic>\n                      deficiency had no significant effect on luciferase expression when it was under the control of the intact\n                      <jats:italic toggle=\"yes\">brpA<\/jats:italic>\n                      promoter, but the reporter activity increased by &gt;6-fold (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001) when the reporter gene was fused to a\n                      <jats:italic toggle=\"yes\">brpA<\/jats:italic>\n                      promoter derivative with deletion of a putative XRE-binding box. Electrophoretic mobility shift assay (EMSA) showed that recombinant XRE interacted with the\n                      <jats:italic toggle=\"yes\">brpA<\/jats:italic>\n                      promoter, resulting in an electrophoretic shift of the promoter probes.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      transcription assay also showed that inclusion of XRE caused transcription to fall off, significantly reducing full-length\n                      <jats:italic toggle=\"yes\">brpA<\/jats:italic>\n                      transcripts. RNA-seq analysis revealed that deficiency of XRE led to altered expression of &gt;102 genes by &gt;2-fold (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05), including 28 with increased expression, and 74 with decreased expression. Among the down-regulated were genes for DNA repair and oxidative stress tolerance response. These results suggest that XRE (SMU.405c) in\n                      <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                      plays an important role in\n                      <jats:italic toggle=\"yes\">brpA<\/jats:italic>\n                      expression and oxidative stress tolerance response.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>\n                        <jats:bold>IMPORTANCE<\/jats:bold>\n                      <\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Streptococcus mutans<\/jats:italic>\n                        , a keystone pathogen in human dental caries, primarily lives in the highly diverse microbiota on tooth surfaces, where the conditions are often harsh and fluctuate frequently. Locus SMU.405c was annotated to encode a xenobiotic response element (XRE)-like transcriptional regulator, but no information is available concerning the role of this protein in\n                        <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                        pathophysiology. This study used a functional genomics approach along with molecular and transcriptomic analysis to characterize a deletional\n                        <jats:italic toggle=\"yes\">xre<\/jats:italic>\n                        mutant, and the results showed that\n                        <jats:italic toggle=\"yes\">xre<\/jats:italic>\n                        deficiency in\n                        <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                        resulted in weakened oxidative stress tolerance response and alterations in transcription of &gt;102 genes, including those known to play an important role in cell envelope biogenesis and stress tolerance response. Reporter fusion assay, electrophoretic mobility shift assay (EMSA), and\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        transcription further demonstrated that the XRE-like regulator encoded by SMU.405c is a repressor of\n                        <jats:italic toggle=\"yes\">brpA<\/jats:italic>\n                        expression and plays an important role in oxidative stress tolerance response.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.00116-26","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:00:20Z","timestamp":1784638820000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["An XRE-type regulator in\n                    <i>Streptococcus mutans<\/i>\n                    plays an important role in\n                    <i>brpA<\/i>\n                    expression and oxidative stress tolerance response"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8540-3420","authenticated-orcid":true,"given":"Zezhang T.","family":"Wen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01qv8fp92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center","place":["New Orleans, USA"]},{"id":[{"id":"https:\/\/ror.org\/01qv8fp92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, Immunology and Parasitology, School of Medicine, Louisiana State University Health Sciences Center","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-9807","authenticated-orcid":false,"given":"Kassapa","family":"Ellepola","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01qv8fp92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Guillot","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01qv8fp92","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center","place":["New Orleans, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8268-1601","authenticated-orcid":false,"given":"Hemendra P. 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