Biological roles of extracellular proteins in Streptococcus mutans

Streptococcus mutans remains a key etiologic agent of dental caries by thriving in dysbiotic plaque biofilms that sustain low pH and abundant extracellular matrix. Although acidogenesis and extracellular polysaccharide (EPS) synthesis are long recognized virulence traits, accumulating evidence indicates that a coordinated network of extracellular proteins is the operational interface that links carbohydrate metabolism to adhesion, matrix architecture, quorum-guided behaviors, and ecological competition. Here we review major surface-anchored and secreted proteins and peptides that drive cariogenic fitness, including adhesins, glucan-binding proteins, collagen-binding proteins (Cnm/Cbm), the LPXTG display machinery, autolysin-mediated extracellular DNA (eDNA) release, protease control of pheromone maturation, glucosyltransferases, peptide pheromones, and secreted bacteriocins/mutacins. We synthesize emerging concepts on how these factors build composite matrices composed of glucans, proteins, and eDNA, create diffusion-limited acidic microenvironments, and couple competence and bacteriocin programs to community restructuring. We highlight underappreciated layers of regulation, such as matrix-retained signaling, interplay between the competence-stimulating peptide (CSP) and ComX-inducing peptide (XIP) circuits, and enzymes such as SMU_833/RgpI that may tune glucan-eDNA interactions. Beyond the mouth, we discuss evidence that Cnm/Cbm-positive lineages expand tissue tropism and contribute to extra-oral diseases, including infective endocarditis and cardiovascular complications, motivating risk-stratified interventions. Finally, we assess therapeutic opportunities that emphasize anti-virulence and precision strategies targeting extracellular mechanisms while sparing commensals. We conclude by outlining key knowledge gaps and future directions toward integrated anti-biofilm interventions that attenuate S. mutans pathogenicity while preserving commensal-driven oral ecological stability.