Vibrio cholerae cytolysin is composed of an α‐hemolysin‐like core

Abstract

The enteric pathogen Vibrio cholerae secretes a water‐soluble 80‐kD cytolysin, Vibrio cholerae cytolysin (VCC) that assembles into pentameric channels following proteolytic activation by exogenous proteases. Until now, VCC has been placed in a unique class of pore‐forming toxins, distinct from paradigms such as Staphyloccal α‐hemolysin. However, as reported here, amino acid sequence analysis and three‐dimensional structure modeling indicate that the core component of the VCC toxin is related in sequence and structure to a family of hemolysins from Staphylococcus aureus that include leukocidin F and α‐hemolysin. Furthermore, our analysis has identified the channel‐forming region of VCC and a potential lipid head‐group binding site, and suggests a conserved mechanism of assembly and lysis. An additional domain in the VCC toxin is related to plant lectins, conferring additional target cell specificity to the toxin.