ArticleAntimicrobial agents and chemotherapy2011
Development of an antivirulence drug against Streptococcus mutans: repression of biofilm formation, acid tolerance, and competence by a histidine kinase inhibitor, walkmycin C.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 67 citations in OpenAlex.
- Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.Molecular oral microbiology · 2026Review
- Two-component systems as potential therapeutic targets inAnnals of medicine · 2025Review
- Asiatic Acid Disrupts the Biofilm Virulence ofInternational journal of molecular sciences · 2025Article
- Impact of Graphene Layers on Genetic Expression and Regulation within Sulfate-Reducing Biofilms.Microorganisms · 2024Article
- Quorum Quenching Approaches against Bacterial-Biofilm-Induced Antibiotic Resistance.Antibiotics (Basel, Switzerland) · 2024Review
- Bacterial Histidine Kinase and the Development of Its Inhibitors in the 21st Century.Antibiotics (Basel, Switzerland) · 2024Review
- Regulatory mechanisms of exopolysaccharide synthesis and biofilm formation in Streptococcus mutans.Journal of oral microbiology · 2023Review
- Quorum Sensing and Quorum Quenching with a Focus on Cariogenic and Periodontopathic Oral Biofilms.Microorganisms · 2022Review
- Anti-Quorum Sensing Activities of Gliptins againstBiomedicines · 2022Article
- Targeting of Regulators as a Promising Approach in the Search for Novel Antimicrobial Agents.Microorganisms · 2022Article
- Recent Advances in Histidine Kinase-Targeted Antimicrobial Agents.Frontiers in chemistry · 2022Review
- Inhibitors targeting the autophosphorylation of serine/threonine kinase ofFrontiers in microbiology · 2022Article
- The Oral Microbiota: Community Composition, Influencing Factors, Pathogenesis, and Interventions.Frontiers in microbiology · 2022Review
- The W-Acidic Motif of Histidine Kinase WalK Is Required for Signaling and Transcriptional Regulation inFrontiers in microbiology · 2022Article
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- Evaluation of Anti-Biofilm Capability of Cordycepin AgainstInfection and drug resistance · 2021Article
- Polymyxins, the last-resort antibiotics: Mode of action, resistance emergence, and potential solutions.Journal of biosciences · 2021Review
- Natural products as inspiration for the development of bacterial antibiofilm agents.Natural product reports · 2020Review
- Progress Overview of Bacterial Two-Component Regulatory Systems as Potential Targets for Antimicrobial Chemotherapy.Antibiotics (Basel, Switzerland) · 2020Review
- Synthesis of histidine kinase inhibitors and their biological properties.Medicinal research reviews · 2020Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two-component signal transduction systems (TCSs) in prokaryotes often regulate gene clusters that induce pathogenicity, and thus they have frequently been proposed as potential drug targets for attenuating the virulence of pathogens. The pathogenic potential of Streptococcus mutans, the major etiological pathogen of dental caries, is also regulated by its TCSs. The object of this study was to evaluate the effect of a histidine kinase (HK) inhibitor against two major virulence factors of S. mutans: biofilm formation and acid tolerance. Walkmycin C (WKM C), an HK inhibitor isolated from the screening of inhibitors against WalK HK in Bacillus subtilis, inhibited the in vitro autophosphorylation activity of three purified S. mutans HKs, i.e., VicK, CiaH, and LiaS. Although S. mutans does not have any essential HK but only an essential response regulator, VicR, WKM C showed an MIC of 6.25 μg/ml. This inhibitory effect of WKM C suggests that blocking the autophosphorylation of multiple HKs may inhibit phosphotransfer to VicR from VicK and other HKs. When WKM C was added at sub-MIC levels, the cells formed abnormal biofilms and also showed a defect in competence. When the cells were pretreated with WKM C, an increase in acid sensitivity was observed. Our results show that WKM C represses two pathogenic phenotypes of S. mutans, indicating the possibility of developing histidine kinase inhibitors into antivirulence drugs.
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