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

Vibrio cholerae uses the Type VI Secretion System (T6SS) to compete with neighboring bacteria and colonize the gut. The effector VgrG1 contains a C-terminal Actin Crosslinking Domain (VgrG1-ACD) that irreversibly crosslinks eukaryotic actin, disrupting the host cytoskeleton. Whether this domain also functions directly in interbacterial competition was previously unknown. This study identifies MreB, the bacterial actin homolog responsible for cell shape and wall synthesis, as a novel bacterial target of VgrG1-ACD.

Using E. coli as a model, the authors demonstrate that VgrG1-ACD binds specifically to MreB, causing pronounced morphological defects and impaired growth. Unlike its action on mammalian actin, VgrG1-ACD does not crosslink MreB, indicating a distinct mechanism. The discovery reveals a dual-targeting strategy whereby a single T6SS effector manipulates both eukaryotic actin and its bacterial counterpart, potentially enhancing V. cholerae fitness during interbacterial competition and host colonization. These findings broaden the known functional repertoire of VgrG1-ACD beyond host-directed virulence.