{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:31:12Z","timestamp":1787016672173,"version":"build-2736575974"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Sichuan Science and Technology Program","award":["2022NSFSC1482"],"award-info":[{"award-number":["2022NSFSC1482"]}]},{"name":"Sichuan Science and Technology Program","award":["2023NSFSC1509"],"award-info":[{"award-number":["2023NSFSC1509"]}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82170947"],"award-info":[{"award-number":["82170947"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32170046"],"award-info":[{"award-number":["32170046"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Fundamental Research Funds for the Central Universities, Research and Develop Program, West China Hospital of Stomatology Sichuan University","award":["RD-02-202402"],"award-info":[{"award-number":["RD-02-202402"]}]},{"name":"Fundamental Research Funds for the Central Universities, Research and Develop Program, West China Hospital of Stomatology Sichuan University","award":["RD-02-202406"],"award-info":[{"award-number":["RD-02-202406"]}]},{"name":"Research Funding from West China School\/Hospital of Stomatology Sichuan University","award":["RCDWJS2023-10"],"award-info":[{"award-number":["RCDWJS2023-10"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2024,2,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Dental caries is the most common chronic infectious disease around the world and disproportionately affects the marginalized socioeconomic group.\n                      <jats:italic>Streptococcus mutans<\/jats:italic>\n                      , considered a primary etiological agent of caries, depends on the coordinated physiological response to tolerate the oxidative stress generated by commensal species within dental plaque, which is a critical aspect of its pathogenicity. Here, we identified and characterized a novel tetracycline repressor family regulator, SMU_1361c, which appears to be acquired by the bacteria via horizontal gene transfer. Surprisingly,\n                      <jats:italic>smu_1361c<\/jats:italic>\n                      functions as a negative transcriptional regulator to regulate gene expression outside its operon and is involved in the oxidative stress response of\n                      <jats:italic>S. mutans<\/jats:italic>\n                      . The\n                      <jats:italic>smu_1361c<\/jats:italic>\n                      overexpression strain UA159\/pDL278-\n                      <jats:italic>1361c<\/jats:italic>\n                      was more susceptible to oxidative stress and less competitive against hydrogen peroxide generated by commensal species\n                      <jats:italic>Streptococcus gordonii<\/jats:italic>\n                      and\n                      <jats:italic>Streptococcus sanguinis<\/jats:italic>\n                      . Transcriptomics analysis revealed that\n                      <jats:italic>smu_1361c<\/jats:italic>\n                      overexpression resulted in the significant downregulation of 22 genes, mainly belonging to three gene clusters responsible for the oxidative stress response. The conversed DNA binding motif of SMU_1361c was determined by electrophoretic mobility shift and DNase I footprinting assay with purified SMU_1361c protein; therefore,\n                      <jats:italic>smu_1361c<\/jats:italic>\n                      is directly involved in gene transcription related to the oxidative stress response. Crucially, our finding provides a new understanding of how\n                      <jats:italic>S. mutans<\/jats:italic>\n                      deals with the oxidative stress that is required for pathogenesis and will facilitate the development of new and improved therapeutic approaches for dental caries.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic>Streptococcus mutans<\/jats:italic>\n                        is the major organism associated with the development of dental caries, which globally is the most common chronic disease. To persist and survive in biofilms,\n                        <jats:italic>S. mutans<\/jats:italic>\n                        must compete with commensal species that occupy the same ecological niche. Here, we uncover a novel molecular mechanism of how tetracycline repressor family regulator\n                        <jats:italic>smu_1361c<\/jats:italic>\n                        is involved in the oxidative stress response through transcriptomics analysis, electrophoretic mobility shift assay, and DNase I footprinting assay. Furthermore, we demonstrated that\n                        <jats:italic>smu_1361c<\/jats:italic>\n                        mediates\n                        <jats:italic>S. mutans<\/jats:italic>\n                        sensitivity to oxidative stress and competitiveness with commensal streptococci. Therefore, this study has revealed a previously unknown regulation between\n                        <jats:italic>smu_1361c<\/jats:italic>\n                        and genes outside its operon and demonstrated the importance of\n                        <jats:italic>smu<\/jats:italic>\n                        _\n                        <jats:italic>1361c<\/jats:italic>\n                        in the oxidative stress response and the fitness of\n                        <jats:italic>S. mutans<\/jats:italic>\n                        within the plaque biofilms, which can be exploited as a new therapy to modulate ecological homeostasis and prevent dental caries.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/aem.01871-23","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T09:01:01Z","timestamp":1706778061000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["SMU_1361c regulates the oxidative stress response of\n                    <i>Streptococcus mutans<\/i>"],"prefix":"10.1128","volume":"90","author":[{"given":"Shuxing","family":"Yu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4247-0134","authenticated-orcid":false,"given":"Qizhao","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqi","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Gong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5039-4648","authenticated-orcid":false,"given":"Qiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-9672","authenticated-orcid":false,"given":"Jing","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"},{"name":"Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3410-6300","authenticated-orcid":true,"given":"Yuqing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515573272"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.30"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6831-6-S1-S14"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1159\/000324598"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/mr.50.4.353-380.1986"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.03.518"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn1890"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-020-0135-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2012.00325.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034519866440"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0089-x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00535-20"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12147"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16367-5"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00108"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801499105"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01569826"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00456-z"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060839"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22094642"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3032"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020127"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.06812-11"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01499-16"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.659220"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.172501299"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26004-5"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro884"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28647-0"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.03079-09"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.21.7193-7203.2005"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02399-4"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05546.x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.07539-11"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/1462-2920.13123"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520927385"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211000668"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.01272-21"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.12.3770-3783.2001"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.43.11.5721-5732.2005"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-020-00789-7"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2381"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00276-08"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/717843"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01345-17"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0051\u20132018"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.69.2.326-356.2005"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00018-13"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.06122-11"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00508-20"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.02390-21"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/0147-619x(92)90044-b"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010134"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.06362-11"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12350"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.57.4.1134-1138.1991"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02013-22"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41396-020-0592-8"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/mSystems.00788-21"}],"container-title":["Applied and Environmental Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aem.01871-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/aem.01871-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T19:27:27Z","timestamp":1715801247000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/aem.01871-23"}},"subtitle":[],"editor":[{"given":"Knut","family":"Rudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,2,21]]},"references-count":59,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,21]]}},"alternative-id":["10.1128\/aem.01871-23"],"URL":"https:\/\/doi.org\/10.1128\/aem.01871-23","relation":{},"ISSN":["0099-2240","1098-5336"],"issn-type":[{"value":"0099-2240","type":"print"},{"value":"1098-5336","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,21]]},"assertion":[{"value":"2023-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01871-23"}}