{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:39:56Z","timestamp":1776285596193,"version":"3.50.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T00:00:00Z","timestamp":1737072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32170046"],"award-info":[{"award-number":["32170046"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170947"],"award-info":[{"award-number":["82170947"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32400094"],"award-info":[{"award-number":["32400094"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Streptococcus mutans<\/jats:italic> is a key etiological agent in dental caries, owing to its strong ability to form biofilms through carbohydrate fermentation. Protein acetylation, facilitated by GNAT family acetyltransferases, plays a critical regulatory role in bacterial physiology, but its impact on <jats:italic>S. mutans<\/jats:italic> remains largely unexplored. In this study, we investigated the role of the GNAT family acetyltransferase encoded by <jats:italic>smu_1558c<\/jats:italic> in regulating the growth and biofilm formation of <jats:italic>S. mutans<\/jats:italic>. The deletion of <jats:italic>smu_1558c<\/jats:italic> resulted in impaired growth, reduced biofilm formation, and diminished synthesis of water-insoluble extracellular polysaccharides (EPS). Proteomic analysis revealed 166 differentially expressed proteins in the deletion mutant, with significant enrichment in pathways related to carbohydrate transport and metabolism, and translation. Notably, glucosyltransferases GtfB and GtfC, key enzymes in biofilm formation, were significantly downregulated in the deletion mutant, while ClpL, a Clp-like ATP-dependent protease involved in protein homeostasis under stress conditions, was highly upregulated. These findings highlight that acetyltransferase <jats:italic>smu_1558c<\/jats:italic> plays a crucial role in the growth, biofilm formation, and EPS synthesis of <jats:italic>S. mutans<\/jats:italic> through its regulation of carbohydrate transport and metabolism pathways, as well as stress response mechanisms. This study provides novel insights into the molecular mechanisms governing <jats:italic>S. mutans<\/jats:italic> pathogenicity and suggests potential therapeutic targets for caries prevention.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1507928","type":"journal-article","created":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T06:51:52Z","timestamp":1737096712000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["smu_1558c-mediated regulation of growth and biofilm formation in Streptococcus mutans"],"prefix":"10.3389","volume":"15","author":[{"given":"Jing","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qizhao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingou","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangyang","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuxing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"14434","DOI":"10.1073\/pnas.172501299","article-title":"Genome sequence of Streptococcus mutans UA159, a cariogenic dental pathogen","volume":"99","author":"Ajdic","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3531","DOI":"10.1038\/s41467-023-39316-5","article-title":"A polyamine acetyltransferase regulates the motility and biofilm formation of Acinetobacter baumannii","volume":"14","author":"Armalyt\u0117","year":"2023","journal-title":"Nat. Commun."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"134645","DOI":"10.1016\/j.ijbiomac.2024.134645","article-title":"Targeting glucosyltransferases to combat dental caries: current perspectives and future prospects","volume":"278","author":"Atta","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e00090-19","DOI":"10.1128\/MMBR.00090-19","article-title":"Small-molecule acetylation by GCN5-related N-acetyltransferases in Bacteria","volume":"84","author":"Burckhardt","year":"2020","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e00107-17","DOI":"10.1128\/JB.00107-17","article-title":"Regulation, function, and detection of protein acetylation in Bacteria","volume":"199","author":"Carabetta","year":"2017","journal-title":"J. Bacteriol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1177\/00220345211000668","article-title":"EpsR negatively regulates Streptococcus mutans exopolysaccharide synthesis","volume":"100","author":"Chen","year":"2021","journal-title":"J. Dent. Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e02708-18","DOI":"10.1128\/mBio.02708-18","article-title":"Mechanisms, detection, and relevance of protein acetylation in prokaryotes","volume":"10","author":"Christensen","year":"2019","journal-title":"MBio"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1177\/0022034519845001","article-title":"The role of exopolysaccharides in Oral biofilms","volume":"98","author":"Cugini","year":"2019","journal-title":"J. Dent. Res."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1146\/annurev.biochem.73.011303.073626","article-title":"ATP-binding cassette transporters in bacteria","volume":"73","author":"Davidson","year":"2004","journal-title":"Annu. Rev. Biochem."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e20200733","DOI":"10.1590\/1678-7757-2020-0733","article-title":"Effects of ClpP protease on biofilm formation of Enterococcus faecalis","volume":"29","author":"Feng","year":"2021","journal-title":"J. Appl. Oral Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1111\/j.1365-2958.2004.04368.x","article-title":"Clp ATPases are required for stress tolerance, intracellular replication and biofilm formation in Staphylococcus aureus","volume":"54","author":"Frees","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e0078821","DOI":"10.1128\/mSystems.00788-21","article-title":"Transcriptional profiling reveals the importance of RcrR in the regulation of multiple sugar transportation and biofilm formation in Streptococcus mutans","volume":"6","author":"Gong","year":"2021","journal-title":"mSystems"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.bbrc.2018.12.071","article-title":"The regulation of Porphyromonas gingivalis biofilm formation by ClpP","volume":"509","author":"He","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.jdsr.2022.10.003","article-title":"The findings of glucosyltransferase enzymes derived from oral streptococci","volume":"58","author":"Hoshino","year":"2022","journal-title":"Jpn. Dent. Sci. Rev."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1016\/j.drudis.2021.05.014","article-title":"Recent advances in Clp protease modulation to address virulence, resistance and persistence of MRSA infection","volume":"26","author":"Ju","year":"2021","journal-title":"Drug Discov. Today"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fcimb.2015.00010","article-title":"Streptococcus mutans-derived extracellular matrix in cariogenic oral biofilms","volume":"5","author":"Klein","year":"2015","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1177\/0022034513504218","article-title":"The exopolysaccharide matrix: a virulence determinant of cariogenic biofilm","volume":"92","author":"Koo","year":"2013","journal-title":"J. Dent. Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1038\/s41579-018-0089-x","article-title":"The oral microbiota: dynamic communities and host interactions","volume":"16","author":"Lamont","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref7001","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/0147-619x(92)90044-b","article-title":"Molecular, genetic, and functional analysis of the basic replicon of pVA380-1, a plasmid of oral streptococcal origin","volume":"28","author":"LeBlanc","year":"1992","journal-title":"Plasmid."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3389\/fmicb.2018.00030","article-title":"Substrate binding protein DppA1 of ABC transporter DppBCDF increases biofilm formation in Pseudomonas aeruginosa by inhibiting Pf5 prophage lysis","volume":"9","author":"Lee","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"167","DOI":"10.21775\/cimb.032.167","article-title":"The VicRK two-component system regulates Streptococcus mutans virulence","volume":"32","author":"Lei","year":"2019","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"3224","DOI":"10.3389\/fmicb.2018.03224","article-title":"A GntR family transcription factor in Streptococcus mutans regulates biofilm formation and expression of multiple sugar transporter genes","volume":"9","author":"Li","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1093\/mmy\/myz043","article-title":"The histone acetyltransferase GcnE regulates conidiation and biofilm formation in Aspergillus fumigatus","volume":"58","author":"Lin","year":"2020","journal-title":"Med. Mycol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"107842","DOI":"10.1016\/j.biotechadv.2021.107842","article-title":"Bacterial protein acetylation and its role in cellular physiology and metabolic regulation","volume":"53","author":"Liu","year":"2021","journal-title":"Biotechnol. Adv."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3352","DOI":"10.1074\/mcp.M114.041962","article-title":"Acetylome analysis reveals diverse functions of lysine acetylation in Mycobacterium tuberculosis","volume":"13","author":"Liu","year":"2014","journal-title":"Mol. Cell. Proteomics"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1111\/j.2041-1014.2012.00641.x","article-title":"The Pst system of Streptococcus mutans is important for phosphate transport and adhesion to abiotic surfaces","volume":"27","author":"Luz","year":"2012","journal-title":"Mol Oral Microbiol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"e0201322","DOI":"10.1128\/mbio.02013-22","article-title":"Acetylation of lactate dehydrogenase negatively regulates the Acidogenicity of Streptococcus mutans","volume":"13","author":"Ma","year":"2022","journal-title":"MBio"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e1010134","DOI":"10.1371\/journal.ppat.1010134","article-title":"Acetylation of glucosyltransferases regulates Streptococcus mutans biofilm formation and virulence","volume":"17","author":"Ma","year":"2021","journal-title":"PLoS Pathog."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"784923","DOI":"10.3389\/fmicb.2021.784923","article-title":"Post-translational modifications in Oral Bacteria and their functional impact","volume":"12","author":"Ma","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1111\/mmi.14649","article-title":"ClpP1P2 peptidase activity promotes biofilm formation in Pseudomonas aeruginosa","volume":"115","author":"Mawla","year":"2021","journal-title":"Mol. Microbiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41580-018-0081-3","article-title":"Functions and mechanisms of non-histone protein acetylation","volume":"20","author":"Narita","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"208","DOI":"10.4236\/aim.2012.23025","article-title":"Biofilm formation by Streptococcus mutans and related Bacteria","volume":"2","author":"Nishimura","year":"2012","journal-title":"Adv. Microbiol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1111\/febs.13228","article-title":"ClpL is a chaperone without auxiliary factors","volume":"282","author":"Park","year":"2015","journal-title":"FEBS J."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"17030","DOI":"10.1038\/nrdp.2017.30","article-title":"Dental caries","volume":"3","author":"Pitts","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.tim.2017.04.001","article-title":"Protein acetylation and its role in bacterial virulence","volume":"25","author":"Ren","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1177\/0022034517742139","article-title":"Resilience of the Oral microbiota in health: mechanisms that prevent Dysbiosis","volume":"97","author":"Rosier","year":"2018","journal-title":"J. Dent. Res."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1111\/prd.12354","article-title":"Omics and interspecies interaction","volume":"85","author":"Shokeen","year":"2021","journal-title":"Periodontol. 2000"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41580-021-00441-y","article-title":"Modulation of cellular processes by histone and non-histone protein acetylation","volume":"23","author":"Shvedunova","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.tim.2014.10.010","article-title":"Solving the etiology of dental caries","volume":"23","author":"Sim\u00f3n-Soro","year":"2015","journal-title":"Trends Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1080\/22221751.2020.1714488","article-title":"ATP-binding cassette (ABC) import systems of Mycobacterium tuberculosis: target for drug and vaccine development","volume":"9","author":"Soni","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1080\/22221751.2019.1656549","article-title":"Comprehensive analysis of the lysine acetylome in Aeromonas hydrophila reveals cross-talk between lysine acetylation and succinylation in LuxS","volume":"8","author":"Sun","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"2061","DOI":"10.1128\/AEM.71.4.2061-2069.2005","article-title":"Characterization of a mobile clpL gene from Lactobacillus rhamnosus","volume":"71","author":"Suokko","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1177\/154405910408301110","article-title":"Synergistic effects of streptococcal glucosyltransferases on adhesive biofilm formation","volume":"83","author":"Tamesada","year":"2004","journal-title":"J. Dent. Res."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1111\/j.2041-1014.2010.00585.x","article-title":"Using DGGE profiling to develop a novel culture medium suitable for oral microbial communities","volume":"25","author":"Tian","year":"2010","journal-title":"Mol Oral Microbiol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1146\/annurev-micro-020518-115526","article-title":"Protein acetylation in Bacteria","volume":"73","author":"VanDrisse","year":"2019","journal-title":"Ann. Rev. Microbiol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1111\/omi.12264","article-title":"EzrA, a cell shape regulator contributing to biofilm formation and competitiveness in Streptococcus mutans","volume":"34","author":"Xiang","year":"2019","journal-title":"Mol Oral Microbiol"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"e1002623","DOI":"10.1371\/journal.ppat.1002623","article-title":"The exopolysaccharide matrix modulates the interaction between 3D architecture and virulence of a mixed-species oral biofilm","volume":"8","author":"Xiao","year":"2012","journal-title":"PLoS Pathog."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"8025","DOI":"10.1128\/AEM.06362-11","article-title":"Cloning-independent and counterselectable markerless mutagenesis system in Streptococcus mutans","volume":"77","author":"Xie","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1128\/AAC.01016-10","article-title":"The tea catechin epigallocatechin gallate suppresses cariogenic virulence factors of Streptococcus mutans","volume":"55","author":"Xu","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e1096","DOI":"10.1002\/mbo3.1096","article-title":"Small noncoding RNA sRNA0426 is involved in regulating biofilm formation in Streptococcus mutans","volume":"9","author":"Yin","year":"2020","journal-title":"Microbiology"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"e0187123","DOI":"10.1128\/aem.01871-23","article-title":"SMU_1361c regulates the oxidative stress response of Streptococcus mutans","volume":"90","author":"Yu","year":"2024","journal-title":"Appl. Environ. Microbiol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1007\/s00284-015-0779-9","article-title":"ClpP affects biofilm formation of Streptococcus mutans differently in the presence of cariogenic carbohydrates through regulating gtfBC and ftf","volume":"70","author":"Zhang","year":"2015","journal-title":"Curr. Microbiol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1038\/s41368-021-00137-1","article-title":"Molecular mechanisms of inhibiting glucosyltransferases for biofilm formation in Streptococcus mutans","volume":"13","author":"Zhang","year":"2021","journal-title":"Int. J. Oral Sci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12866-020-1719-9","article-title":"ClpP participates in stress tolerance, biofilm formation, antimicrobial tolerance, and virulence of Enterococcus faecalis","volume":"20","author":"Zheng","year":"2020","journal-title":"BMC Microbiol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1507928\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T06:51:54Z","timestamp":1737096714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1507928\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":54,"alternative-id":["10.3389\/fmicb.2024.1507928"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1507928","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]},"article-number":"1507928"}}