Flagella-mediated secretion of a novel Vibrio cholerae cytotoxin affecting both vertebrate and invertebrate hosts

Abstract

Using <i>Caenorhabditis elegans</i> as an infection host model for <i>Vibrio cholerae</i> predator interactions, we discovered a bacterial cytotoxin, MakA, whose function as a virulence factor relies on secretion via the flagellum channel in a proton motive force-dependent manner. The MakA protein is expressed from the polycistronic <i>makDCBA</i> (<i>m</i>otility-<i>a</i>ssociated <i>k</i>illing factor) operon. Bacteria expressing <i>makDCBA</i> induced dramatic changes in intestinal morphology leading to a defecation defect, starvation and death in <i>C. elegans</i>. The Mak proteins also promoted <i>V. cholerae</i> colonization of the zebrafish gut causing lethal infection. A structural model of purified MakA at 1.9 Å resolution indicated similarities to members of a superfamily of bacterial toxins with unknown biological roles. Our findings reveal an unrecognized role for <i>V. cholerae</i> flagella in cytotoxin export that may contribute both to environmental spread of the bacteria by promoting survival and proliferation in encounters with predators, and to pathophysiological effects during infections.