{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T07:56:48Z","timestamp":1772697408359,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Streptococcus mutans<\/jats:italic>\n                      (\n                      <jats:italic>S. mutans<\/jats:italic>\n                      ) is a primary cariogenic pathogen responsible for acid production, exopolysaccharides (EPS) production and biofilm formation. Two-component systems (TCS) regulate EPS metabolism, especially the VicRK TCS. Overexpression of antisense\n                      <jats:italic>vicR<\/jats:italic>\n                      (AS\n                      <jats:italic>vicR<\/jats:italic>\n                      ) can reduce EPS production and thereby weaken the cariogenicity of\n                      <jats:italic>S. mutans.<\/jats:italic>\n                      Although the antimicrobial monomer dimethylaminohexadecyl methacrylate (DMAHDM) exhibits potent antibacterial properties, mature\n                      <jats:italic>S. mutans<\/jats:italic>\n                      biofilms can protect themselves by extracellular matrix. Emerging evidence suggests that genetic intervention enhances drug efficacy, yet the underlying regulatory mechanisms remain largely unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To investigate the chemical\u2013genetic cooperative antibiofilm strategy inhibition and mechanisms of AS\n                      <jats:italic>vicR<\/jats:italic>\n                      overexpression combined with DMAHDM on\n                      <jats:italic>S. mutans<\/jats:italic>\n                      biofilm formation, acid and EPS metabolism, and cariogenicity through the VicRK system.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The minimal inhibitory concentration and minimal bactericidal concentration of DMAHDM and chlorhexidine were determined. Biofilm properties were evaluated via biomass assessment, EPS quantification, lactate production measurement, and colony-forming unit counting. Biofilm structures were examined by scanning electron microscopy. Mechanisms were investigated using RT-qPCR, zymography, and western blot. Rat caries model was employed to assess caries formation under different treatment conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The AS\n                      <jats:italic>vicR<\/jats:italic>\n                      strain exhibited an approximate 2-fold increase in susceptibility to DMAHDM and chlorhexidine. The combination treatment reduced biofilm CFU by approximately 4 log units, significantly lowered lactate and EPS levels, and resulted in a loose, porous biofilm structure. The expression levels of cariogenic virulence factors as well as the VicRK TCS genes and proteins were significantly downregulated.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , the combined treatment reduced the overall caries severity score to 12.7% of the control group (p&amp;lt;0.05) without observing any systemic adverse effects.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The strategy of combining AS\n                      <jats:italic>vicR<\/jats:italic>\n                      overexpression with DMAHDM effectively modulates EPS metabolism and cariogenicity in\n                      <jats:italic>S. mutans<\/jats:italic>\n                      by interfering with the VicRK TCS, providing a potential therapeutic approach for clinical caries management.\n                    <\/jats:p>\n 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