The transcription factor LafI integrates control of flagellar motility and T3SS1-mediated virulence in Vibrio parahaemolyticus

Vibrio parahaemolyticus, a major marine pathogen, employs sophisticated regulatory networks to coordinate motility and virulence during infection, yet the mechanisms remain poorly understood. Here, we identified LafI , a previously uncharacterized transcriptional regulator that represses both motility and virulence in V. parahaemolyticus by governing a regulatory circuit between the lateral flagellar system and type III secretion system 1 (T3SS1). We demonstrated that LafI negatively regulates the motility of V. parahaemolyticus by inhibiting the expression of both the polar and lateral flagellar systems, while it represses T3SS1-mediated cytotoxicity via the master T3SS1 activator ExsA. Furthermore, we revealed a regulatory circuit wherein LafI represses the lateral flagellar master regulator LafK L , which in turn modulates T3SS1 activity through the master activator ExsA, with the latter providing feedback to fine-tune the lateral flagellar system, thereby coordinating V. parahaemolyticus virulence and motility. Our work established LafI as a central regulator that couples motility and virulence, offering new insights into bacterial pathogenesis. IMPORTANCE Pathogens like Vibrio parahaemolyticus , a common cause of seafood-related gastroenteritis, use flagella to move and spread. Although the motilities help bacteria infect hosts, some V. parahaemolyticus clinical isolates display swarming deficiency in vitro while retaining pathogenicity in vivo . The mechanisms by which V. parahaemolyticus strains regulate motility and virulence remain unclear. Here, we identified LafI , a previously uncharacterized transcriptional regulator that represses motility and cytotoxicity through a regulatory circuit between the flagellar systems and T3SS1. Our work shows how V. parahaemolyticus coordinates motility and virulence to adapt to different environments and provides new insight into the interplay between these critical bacterial processes.