Pathogenesis of Porphyromonas gingivalis peptidylarginine deiminase: from periodontal microenvironment to systemic diseases.

Periodontitis is a globally prevalent chronic inflammatory disease that exerts profound effects on both oral and systemic health. Porphyromonas gingivalis is a key pathogenic bacterium in periodontitis. Its secreted peptidylarginine deiminase (PPAD) is a unique protein-citrullinating enzyme. It catalyzes the citrullination of arginine residues in proteins, thereby altering protein structure and function. This review systematically integrates current evidence to elucidate the enzymatic properties, secretion regulatory mechanisms, and pathogenic roles of PPAD in the periodontal microenvironment and distant organs. PPAD serves as a critical driver of periodontitis progression. It also acts as a molecular bridge linking oral infection to remote pathologies. This bridging effect is achieved through outer membrane vesicle-mediated systemic dissemination. PPAD-mediated citrullination constitutes a central nexus connecting this chronic oral infection with various comorbidities, providing a theoretical basis for the development of PPAD-targeted anti-virulence therapeutic strategies against periodontitis and its associated systemic conditions.