Quorum sensing in oral multispecies biofilms: from interkingdom communication to therapeutic targeting

Abstract

Oral biofilms are polymicrobial ecosystems where quorum sensing (QS) governs community assembly, virulence and homeostasis. This narrative review synthesizes evidence on QS pathways in key periodontal and cariogenic pathogens, emphasizing interspecies synergy, cross-kingdom interactions, and disease progression. We surveyed English-language publications up to 2026 across PubMed, Web of Science, and Scopus. Our analysis reveals three major QS circuits: the widely conserved LuxS/AI-2 system facilitating cooperative and competitive behaviors, such as Fusobacterium nucleatum-red complex coaggregation and Veillonella-mediated inhibition; Gram-positive oligopeptide systems (e.g., CSP (competence-stimulating peptide) /ComDE in Streptococcus mutans) governing competence and bacteriocin production; and the specialized acyl-homoserine lactone (AHL/AI-1) system in Gram-negative species, which fine-tunes biofilm maturation, heme acquisition, and interkingdom signaling. Beyond these canonical pathways, recent evidence has revised key assumptions: AI-2 production in Fusobacterium nucleatum is subspecies-specific and uncoupled from QS, while LuxS in Porphyromonas gingivalis exerts AI-2-independent effects on host immune modulation. These findings suggest that QS-inhibitor strategies must account for subspecies-level heterogeneity and distinguish signaling effects to inform targeted design. Pathogenically, QS drives alveolar bone resorption, macrophage-mediated inflammation, and metabolic crosstalk. Therapeutically, diverse QS-inhibitors including natural polyphenols, synthetic small molecules, and AHL-lactonases have indicated promising antibiofilm efficacy in vitro and in animal models. However, clinical translation remains hampered by poor oral retention, safety uncertainties, and a lack of standardized endpoints. We conclude that QS represents a potential druggable vulnerability in oral biofilms, but future efforts must prioritize high-specificity inhibitors, combination regimens with conventional antibiotics, and rigorous in vivo validation to bridge the translational gap.