Dual-function regulator SlmA promotes Vibrio cholerae intestinal colonization by inducing elongation and activating TCP expression

Vibrio cholerae , the etiological agent of cholera, remains a significant global health threat. A key aspect underlying its pathogenic success is morphological plasticity, which enables rapid adaptation to host environments. However, the relationship between morphology and pathogenicity is not fully understood. Elucidating regulation networks is essential for understanding V. cholerae colonization and developing interventions. In this study, we demonstrate that V. cholerae undergoes substantial elongation during infection, and elongated morphology is associated with enhanced bacterial adhesion and colonization. Mechanistically, we identify the multifunctional regulator SlmA as a critical regulator connecting bacterial morphological adaptation to pathogenicity. SlmA regulates the expression of the tcp cluster, which encodes the toxin-coregulated pilus required for efficient colonization, by directly binding to the tcpA promoter region. Furthermore, we revealed that specific point mutations (Thr31, Glu43) of SlmA impair the DNA binding and tcpA regulation without affecting bacterial elongation. Collectively, these findings demonstrate that SlmA promotes bacterial elongation, while enhancing colonization by upregulating tcpA expression, thereby increasing TCP abundance on the bacterial surface. Our study highlights that SlmA plays a critical role in the pathogenic strategy of V. cholerae , coordinating both bacterial morphology and colonization adaptation for successful host infection and cholera pathogenesis.