Exploratory Study of Virulence Factors and Protein–Protein Interaction Networks in Major Oral Pathogens

Introduction: Periodontitis is a prevalent inflammatory disease driven by dysbiotic microbial consortia. Red-complex pathogens ( Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia ) and emerging taxa ( Filifactor alocis and Aggregatibacter actinomycetemcomitans ) are central contributors, yet their virulence mechanisms remain incompletely defined. Objective: To construct protein–protein interaction (PPI) networks of key periodontopathogens and identify conserved as well as pathogen-specific virulence hubs. Methodology: High-confidence PPI networks were generated for 1136 proteins across the five pathogens. Network topology was analyzed to identify hubs, and enrichment analyses were performed to map functional clusters. Results: Hub proteins such as guaA, metG, pheT, lysS, thrA, rplA, purD, and rpsH demonstrated significant interactions with accessory proteins. Conserved hubs, including guaA and ileS, were shared across pathogens and were essential in purine biosynthesis and aminoacyl-tRNA ligation. Pathogen-specific hubs comprised gingipains ( P. gingivalis ), leukotoxin ( A. actinomycetemcomitans ), and dentilisin ( T. denticola ). Functional clustering revealed adhesion, peptidoglycan biosynthesis, and immune modulation pathways. Conclusion: PPI networks provide system-level mechanistic insights into pathogen virulence, revealing conserved vulnerabilities and species-specific mechanisms.