Submitted:
29 October 2026
Posted:
30 October 2026
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Abstract
Dental caries is a multifactorial disease mediated by a microbial biofilm, and it arises from the interaction of microbial metabolism, host defense mechanisms, salivary homeostasis and the mineral stability of enamel. Here we propose a multilevel molecular concept in which resistance to caries is defined by the capacity of the enamel–saliva–immunity–microbiome system to maintain mineral balance and to restore homeostasis after repeated acid loads. We identify seven interconnected functional nodes that determine the cariogenic activity of the biofilm: adhesion, synthesis of the extracellular matrix, acid production, acid tolerance, regulatory signaling, formation of alkaline metabolites, and interspecies metabolic cooperation. The key molecular mechanisms include the SpaP/PAc adhesins, the glucosyltransferases GtfB/GtfC/GtfD, phosphotransferase systems, lactate dehydrogenase, the F₁F₀-ATPase and the regulatory networks VicRK, LiaFSR, ComCDE/ComRS and CcpA. These processes are counteracted by salivary buffering systems, secretory IgA, antimicrobial proteins and microbial alkali-generating mechanisms, above all the arginine deiminase system and urease. We integrate molecular strategies directed at these vulnerabilities, including apigenin, tt-farnesol, epigallocatechin gallate, proanthocyanidins, structure-guided glucosyltransferase inhibitors, selective antimicrobial peptides (C16G2), arginine, fluoride and antigen-specific immunological approaches. We hypothesize that cariogenicity arises from a compensatory molecular network whose vulnerability depends on environmental conditions, metabolic redundancy and the spatial organization of the biofilm. Coordinated modulation of complementary targets may therefore suppress cariogenic functions more effectively than isolated blockade of single targets, while preserving the beneficial activity of the microbial community. The concept links molecular vulnerabilities with microbiome ecological resilience and enamel protection and yields experimentally testable predictions for multi-target caries prevention.
Keywords:
caries resistance
; cariogenic biofilm
; molecular targets
; glucosyltransferases
; acid tolerance
; bacterial signaling
; salivary immunity
; arginine deiminase system
; antivirulence therapy
; ecological resilience
; multi-target intervention
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