Vibrio cholerae VgrG1-ACD Targets E. coli MreB and Regulates Cellular Morphology.

Vibrio cholerae employs the Type VI Secretion System (T6SS) to outcompete neighboring bacteria and establish successful colonization within the polymicrobial gut. The T6SS effector VgrG1 contains a C-terminal Actin Crosslinking Domain (VgrG1-ACD), well known for irreversibly crosslinking eukaryotic actin to disrupt the host cytoskeleton. However, whether VgrG1-ACD also contributes directly to interbacterial competition has remained unexplored. Here, we identify a previously unrecognized bacterial target of VgrG1-ACD: MreB, the bacterial actin homolog essential for cell shape, cell wall synthesis, and cytoskeletal organization. We demonstrate that VgrG1-ACD specifically binds Escherichia coli MreB, resulting in pronounced morphological defects and impaired bacterial growth. Notably, unlike its activity toward mammalian actin, VgrG1-ACD targets MreB without crosslinking it, revealing a distinct mode of action. These findings expand the functional repertoire of VgrG1-ACD beyond host-directed virulence and uncover a dual-targeting strategy through which a single T6SS effector manipulates both mammalian actin and its bacterial homolog, likely enhancing V. cholerae fitness during interbacterial competition and host colonization.