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Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.

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Τίτλος: Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.
Συγγραφείς: Snigdha NT; Department of Dental Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.; Department of Orthodontics, Pedodontics, and Preventive Dentistry, Faculty of Dentistry, Ibn Al-Nafis University, Sanaa, Republic of Yemen., Alamoudi RA; Professor and Consultant of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia., Alghamdi NS; Department Restorative Dental Science, College of Dentistry, King Khalid University, Abha, Saudi Arabia., Kader MA; Department Restorative Dental Science, College of Dentistry, King Khalid University, Abha, Saudi Arabia., Basheer SN; Department of Restorative Dental Sciences, College Of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia., Mulla M; Associate Professor, Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia., Mulla M; Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India., Mathur A; Department of Dental Research Cell, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pimpri, India., Karobari MI; Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.; Faculty of Dentistry, University of Puthisastra, Phnom Penh, Cambodia.
Πηγή: Molecular oral microbiology [Mol Oral Microbiol] 2026 Oct; Vol. 41 (5), pp. 241-257. Date of Electronic Publication: 2026 Jun 24.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: John Wiley & Sons Country of Publication: Denmark NLM ID: 101524770 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2041-1014 (Electronic) Linking ISSN: 20411006 NLM ISO Abbreviation: Mol Oral Microbiol Subsets: MEDLINE
Imprint Name(s): Original Publication: Copenhagen : John Wiley & Sons
Ιατρικοί όροι (MeSH): Biofilms*/growth & development , Streptococcus mutans*/genetics , Streptococcus mutans*/pathogenicity , Streptococcus mutans*/physiology , Bacterial Proteins*/genetics , Bacterial Proteins*/metabolism, Virulence/genetics ; Signal Transduction/genetics ; Dental Caries/microbiology ; Gene Expression Regulation, Bacterial ; Humans ; Oxidative Stress
Περίληψη: Streptococcus mutans 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 VicRK and LiaSR two-component 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 VicRK and LiaSR in the control of S. mutans pathogenicity. VicRK 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-phosphorylation 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 S. mutans to survive different pHs, oxidative bursts, lack of nutrients and chemical disinfection in and outside the mouth. According to mutant, knockout and multi-omics studies, these TCSs are critical for biofilm formation, EPS structures, antimicrobial tolerance and interspecies interactions, including synergistic virulence in mixed-species biofilms. As interest in anti-virulence therapeutics grows, drug targets VicRK and LiaSR have emerged. Potential candidates for the selective disruption of TCS signalling that are unlikely to induce resistance include small-molecule inhibitors, marine-derived 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-mediated virulence with available strategies to address it, this review offers a comprehensive overview of this topic.
(© 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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Contributed Indexing: Keywords: LiaSR; Streptococcus mutans; VicRK; biofilm; dental caries; endodontics; two‐component system
Substance Nomenclature: 0 (Bacterial Proteins)
Entry Date(s): Date Created: 20260624 Date Completed: 20260902 Latest Revision: 20260904
Update Code: 20260904
PubMed Central ID: PMC13535910
DOI: 10.1111/omi.70035
PMID: 42338295
Βάση Δεδομένων: MEDLINE
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  Data: Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.
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  Data: <searchLink fieldCode="AU" term="%22Snigdha+NT%22">Snigdha NT</searchLink>; Department of Dental Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.; Department of Orthodontics, Pedodontics, and Preventive Dentistry, Faculty of Dentistry, Ibn Al-Nafis University, Sanaa, Republic of Yemen.<br /><searchLink fieldCode="AU" term="%22Alamoudi+RA%22">Alamoudi RA</searchLink>; Professor and Consultant of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.<br /><searchLink fieldCode="AU" term="%22Alghamdi+NS%22">Alghamdi NS</searchLink>; Department Restorative Dental Science, College of Dentistry, King Khalid University, Abha, Saudi Arabia.<br /><searchLink fieldCode="AU" term="%22Kader+MA%22">Kader MA</searchLink>; Department Restorative Dental Science, College of Dentistry, King Khalid University, Abha, Saudi Arabia.<br /><searchLink fieldCode="AU" term="%22Basheer+SN%22">Basheer SN</searchLink>; Department of Restorative Dental Sciences, College Of Dentistry, Jazan University, Jazan, Kingdom of Saudi Arabia.<br /><searchLink fieldCode="AU" term="%22Mulla+M%22">Mulla M</searchLink>; Associate Professor, Department of Public Health, College of Applied Medical Sciences, Qassim University, Buraydah, Saudi Arabia.<br /><searchLink fieldCode="AU" term="%22Mulla+M%22">Mulla M</searchLink>; Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.<br /><searchLink fieldCode="AU" term="%22Mathur+A%22">Mathur A</searchLink>; Department of Dental Research Cell, Dr. D. Y. Patil Dental College & Hospital, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pimpri, India.<br /><searchLink fieldCode="AU" term="%22Karobari+MI%22">Karobari MI</searchLink>; Department of Conservative Dentistry and Endodontics, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India.; Faculty of Dentistry, University of Puthisastra, Phnom Penh, Cambodia.
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  Data: <searchLink fieldCode="JN" term="%22101524770%22">Molecular oral microbiology</searchLink> [Mol Oral Microbiol] 2026 Oct; Vol. 41 (5), pp. 241-257. <i>Date of Electronic Publication: </i>2026 Jun 24.
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  Data: Journal Article; Review
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  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22John+Wiley+%26+Sons%22">John Wiley & Sons </searchLink><i>Country of Publication: </i>Denmark <i>NLM ID: </i>101524770 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>2041-1014 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2220411006%22">20411006 </searchLink><i>NLM ISO Abbreviation: </i>Mol Oral Microbiol <i>Subsets: </i>MEDLINE
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  Data: <i>Original Publication</i>: Copenhagen : John Wiley & Sons
– Name: SubjectMESH
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  Data: <searchLink fieldCode="MM" term="%22Biofilms%22">Biofilms*</searchLink>/<searchLink fieldCode="MM" term="%22Biofilms+growth+%26+development%22">growth & development</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+mutans%22">Streptococcus mutans*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+mutans+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+mutans%22">Streptococcus mutans*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+mutans+pathogenicity%22">pathogenicity</searchLink> <br /><searchLink fieldCode="MM" term="%22Streptococcus+mutans%22">Streptococcus mutans*</searchLink>/<searchLink fieldCode="MM" term="%22Streptococcus+mutans+physiology%22">physiology</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Bacterial+Proteins%22">Bacterial Proteins*</searchLink>/<searchLink fieldCode="MM" term="%22Bacterial+Proteins+metabolism%22">metabolism</searchLink><br /><searchLink fieldCode="MH" term="%22Virulence%22">Virulence</searchLink>/<searchLink fieldCode="MH" term="%22Virulence+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Signal+Transduction%22">Signal Transduction</searchLink>/<searchLink fieldCode="MH" term="%22Signal+Transduction+genetics%22">genetics</searchLink> ; <searchLink fieldCode="MH" term="%22Dental+Caries%22">Dental Caries</searchLink>/<searchLink fieldCode="MH" term="%22Dental+Caries+microbiology%22">microbiology</searchLink> ; <searchLink fieldCode="MH" term="%22Gene+Expression+Regulation%2C+Bacterial%22">Gene Expression Regulation, Bacterial</searchLink> ; <searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Oxidative+Stress%22">Oxidative Stress</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Streptococcus mutans 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 VicRK and LiaSR two-component 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 VicRK and LiaSR in the control of S. mutans pathogenicity. VicRK 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-phosphorylation 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 S. mutans to survive different pHs, oxidative bursts, lack of nutrients and chemical disinfection in and outside the mouth. According to mutant, knockout and multi-omics studies, these TCSs are critical for biofilm formation, EPS structures, antimicrobial tolerance and interspecies interactions, including synergistic virulence in mixed-species biofilms. As interest in anti-virulence therapeutics grows, drug targets VicRK and LiaSR have emerged. Potential candidates for the selective disruption of TCS signalling that are unlikely to induce resistance include small-molecule inhibitors, marine-derived 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-mediated virulence with available strategies to address it, this review offers a comprehensive overview of this topic.<br /> (© 2026 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
– Name: Ref
  Label: References
  Group: RefInfo
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  Group:
  Data: <i>Keywords: </i>LiaSR; Streptococcus mutans; VicRK; biofilm; dental caries; endodontics; two‐component system
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  Data: 0 (Bacterial Proteins)
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  Data: <i>Date Created: </i>20260624 <i>Date Completed: </i>20260902 <i>Latest Revision: </i>20260904
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  Data: 10.1111/omi.70035
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        Value: 10.1111/omi.70035
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        Text: English
    PhysicalDescription:
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        StartPage: 241
    Subjects:
      – SubjectFull: Virulence genetics
        Type: general
      – SubjectFull: Signal Transduction genetics
        Type: general
      – SubjectFull: Dental Caries microbiology
        Type: general
      – SubjectFull: Gene Expression Regulation, Bacterial
        Type: general
      – SubjectFull: Humans
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      – SubjectFull: Oxidative Stress
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      – SubjectFull: Streptococcus mutans genetics
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      – SubjectFull: Bacterial Proteins genetics
        Type: general
      – SubjectFull: Bacterial Proteins metabolism
        Type: general
    Titles:
      – TitleFull: Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.
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              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
          Identifiers:
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