Functional divergence and regulatory network of the type VI secretion system in <i>Vibrio parahaemolyticus</i>

ABSTRACT Vibrio parahaemolyticus is a significant marine pathogen causing gastroenteritis and wound infections in humans. Its pathogenicity is mediated by key virulence factors, including the type VI secretion system (T6SS). This review comprehensively synthesizes current knowledge on the functional divergence and regulatory networks of T6SSs in V. parahaemolyticus , with emphasis on T6SS1 and T6SS2. T6SS1, enriched in clinical isolates, is activated under high-salt and warm conditions and primarily facilitates antibacterial competition and adhesion to human epithelial cells in strains such as RIMD2210633. T6SS2, nearly ubiquitous across strains, operates optimally under low-salt/low-temperature conditions and regulates adhesion, biofilm formation, motility, macrophage autophagy induction, and virulence as demonstrated in strains including RIMD2210633 and SH112. Both systems deploy diverse effectors (e.g., Tme1, PoNe, and RhsP) targeting membrane integrity, DNA, or peptidoglycan. Their expression is intricately controlled by environmental cues (e.g., salinity, temperature, and metal ions), stress responses (e.g., antibiotics, ethanol, and curcumin), quorum sensing regulators (e.g., AphA and OpaR), and transcriptional factors (e.g., H-NS, TfoY, and CalR). Strain-specific functional variations highlight the complexity of T6SS biology. Understanding these mechanisms offers insights for developing anti-virulence strategies against V. parahaemolyticus infections.