Virulence diversity among Porphyromonas gingivalis strains: a review of genetic factors
Abstract Background Porphyromonas gingivalis (P. gingivalis) is a Gram-negative anaerobic bacterium and a keystone pathogen in chronic periodontitis. Beyond oral disease, it has been implicated in systemic conditions, including cardiovascular disease, type 2 diabetes, rheumatoid arthritis, and neurodegeneration. Marked strain-to-strain differences in tissue invasion, immune evasion, and pathogenicity suggest that virulence is shaped by complex genetic and regulatory interactions rather than a single determinant. Objective To summarize current knowledge of the genetic diversity of P. gingivalis virulence determinants and their contribution to strain-specific pathogenicity. Design This narrative review synthesizes current evidence on the diversity of major virulence determinants, including fimbriae (FimA and Mfa1), gingipains (RgpA/RgpB/Kgp), Hag-family hemagglutinins, capsular polysaccharide loci, lipopolysaccharide variants, the RagAB nutrient acquisition system, and the type IX secretion system. It also examines the roles of allelic variation, domain rearrangements, phase variation, and horizontal gene transfer in shaping strain-specific virulence repertoires. Conclusions The reviewed evidence indicates that genetic variation across multiple virulence-associated loci contributes to substantial phenotypic diversity among P. gingivalis strains, influencing host interaction, tissue tropism, immune modulation, and pathogenic potential. Integrating comparative genomics with functional phenotyping provides a framework for predicting strain-specific virulence and may facilitate the development of improved diagnostic tools and targeted therapeutic strategies.