LAUSR

Significance Vibrio vulnificus causes life-threatening infections with increasing frequency due to climate change. The transition from intestinal infection to sepsis is linked to a large, secreted toxin that delivers multiple effectors to the cell simultaneously, the most common being the Makes Caterpillars Floppy-like (MCF) domain. MCF causes Golgi dispersion and organelle destruction leading to apoptosis, although the molecular mechanism for cell destruction was unknown. We show MCF cleaves and degrades 50% of all Rab family guanosine triphosphatases (GTPases) in the cell. The mechanism of target selection is uniquely found to be related to Rab structure rather than amino acid sequence variation. Thus, MCF represents an effector strategy to decrease cell viability by broadly targeting Rabs contributing to death from vibriosis.