{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:57:11Z","timestamp":1791946631376,"version":"4.3.4"},"reference-count":92,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oral Microbiology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Streptococcus mutans<\/jats:italic>\n                    is one of the primary causes of dental caries and is often found in persistent endodontic infections, primarily due to its ability to form acidogenic, aciduric and therapeutically recalcitrant biofilms. The\n                    <jats:italic>VicRK<\/jats:italic>\n                    and\n                    <jats:italic>LiaSR<\/jats:italic>\n                    two\u2010component signal transduction systems (TCS) are particularly important regulators of virulence, envelope integrity and stress response. This paper will provide an updated synthesis of the evidence, at the molecular, genetic and systems levels, regarding the architecture, regulation and integration of\n                    <jats:italic>VicRK<\/jats:italic>\n                    and LiaSR in the control of\n                    <jats:italic>S. mutans<\/jats:italic>\n                    pathogenicity.\n                    <jats:italic>VicRK<\/jats:italic>\n                    helps synthesise essential molecules for biofilm formation and reduces the negative impact of environmental stress on microbes. At the same time, LiaSR responds to antimicrobial peptides, oxidative stress, detergents and root canal irrigants by activating membrane repair and protective stress pathways. Structural, transcriptomic and proteomic studies now indicate extensive regulatory overlap, including overlapping promoter targets, cross\u2010phosphorylation and coordinate regulation of autolysins, cell wall biosynthetic enzymes and extracellular DNA (eDNA) release. These systems all work together as part of the signalling. The ability of\n                    <jats:italic>S. mutans<\/jats:italic>\n                    to survive different pHs, oxidative bursts, lack of nutrients and chemical disinfection in and outside the mouth. According to mutant, knockout and multi\u2010omics studies, these TCSs are critical for biofilm formation, EPS structures, antimicrobial tolerance and interspecies interactions, including synergistic virulence in mixed\u2010species biofilms. As interest in anti\u2010virulence therapeutics grows, drug targets\n                    <jats:italic>VicRK<\/jats:italic>\n                    and\n                    <jats:italic>LiaSR<\/jats:italic>\n                    have emerged. Potential candidates for the selective disruption of TCS signalling that are unlikely to induce resistance include small\u2010molecule inhibitors, marine\u2010derived bioactive compounds and computationally designed ligands. The review also highlights translational gaps and stresses the need for advanced delivery platforms, clinical validation and sustainable production of natural inhibitors. By integrating knowledge of the mechanisms underlying TCS\u2010mediated virulence with available strategies to address it, this review offers a comprehensive overview of this topic.\n                  <\/jats:p>","DOI":"10.1111\/omi.70035","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T07:12:33Z","timestamp":1782285153000},"page":"241-257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular Regulation of Virulence and Dental Biofilm Formation in\n                    <i>Streptococcus mutans<\/i>\n                    : Unravelling the Crosstalk Between the\n                    <i>VicRK<\/i>\n                    and\n                    <i>LiaSR<\/i>\n                    Two\u2010Component Systems"],"prefix":"10.1111","volume":"41","author":[{"given":"Niher Tabassum","family":"Snigdha","sequence":"first","affiliation":[{"name":"Department of Dental Research Saveetha Medical College and Hospital Saveetha Institute of Medical and Technical Sciences Saveetha University  Chennai India"},{"name":"Department of Orthodontics Pedodontics, and Preventive Dentistry Faculty of Dentistry Ibn Al\u2010Nafis University  Sanaa Republic of Yemen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-2686","authenticated-orcid":false,"given":"Ruaa Abdullah","family":"Alamoudi","sequence":"additional","affiliation":[{"name":"Professor and Consultant of Endodontics Faculty of Dentistry King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuha Saad","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Department Restorative Dental Science College of Dentistry King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Abdul","family":"Kader","sequence":"additional","affiliation":[{"name":"Department Restorative Dental Science College of Dentistry King Khalid University  Abha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5614-2425","authenticated-orcid":false,"given":"Syed Nahid","family":"Basheer","sequence":"additional","affiliation":[{"name":"Department of Restorative Dental Sciences College Of Dentistry Jazan University  Jazan Kingdom of Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mushir","family":"Mulla","sequence":"additional","affiliation":[{"name":"Associate Professor, Department of Public Health College of Applied Medical Sciences Qassim University  Buraydah Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munaz","family":"Mulla","sequence":"additional","affiliation":[{"name":"Department of Periodontics Saveetha Dental College and Hospitals Saveetha Institute of Medical and Technical Sciences Saveetha University  Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankita","family":"Mathur","sequence":"additional","affiliation":[{"name":"Department of Dental Research Cell Dr. D. 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