Regulatory Role of LuxS-Dependent AI-2 Signaling in Fusobacterium nucleatum subsp. animalis

Fusobacterium nucleatum is a gram-negative, spindle-shaped bacterium that plays a central role in oral biofilms, particularly in periodontal disease-associated subgingival plaque, a polymicrobial community of over 400 bacterial species. It acts as a bridging organism, facilitating the integration of early and late colonizers, a process critical for dental plaque formation. Beyond its ecological role, F. nucleatum is associated with systemic diseases, including preterm birth and colorectal cancer, underscoring its clinical significance.Fusobacterium nucleatum is taxonomically diverse, comprising at least four well-defined subspecies: nucleatum (FNN), polymorphum (FNP), animalis (FNA), and vincentii (FNV). Among these, we found that only FNA strains produce autoinducer-2 (AI-2), a conserved signaling molecule that mediates interspecies communication in both Gram-positive and Gram-negative bacteria. AI-2 biosynthesis depends on the luxS gene, which encodes the enzyme S-ribosylhomocysteinase (LuxS), responsible for generating the AI-2 precursor. Given the role of FNA in colorectal cancer and periodontitis, we investigated how AI-2 production influences the physiology of this subspecies.