A tripartite cytolytic toxin formed by <i>Vibrio cholerae</i> proteins with flagellum-facilitated secretion
Aftab Nadeem, Raghavendra Sashi Krishna Nagampalli, Eric Toh, Athar Alam, Si Lhyam Myint, Thomas Heidler, Mitesh Dongre, Nikola Zlatkov, Hudson Pace, Fouzia Bano, Anders Sjöstedt, Marta Bally, Bernt Eric Uhlin, Sun Nyunt Wai, Karina Persson
Abstract
Significance Vibrio cholerae , responsible for outbreaks of cholera disease, is a highly motile organism by virtue of a single flagellum. We describe how the flagellum facilitates the secretion of three V. cholerae proteins encoded by a hitherto-unrecognized genomic island. The proteins MakA/B/E can form a tripartite toxin that lyses erythrocytes and is cytotoxic to cultured human cells. A structural basis for the cytolytic activity of the Mak proteins was obtained by X-ray crystallography. Flagellum-facilitated secretion ensuring spatially coordinated delivery of Mak proteins revealed a role for the V. cholerae flagellum considered of particular significance for the bacterial environmental persistence. Our findings will pave the way for the development of diagnostics and therapeutic strategies against pathogenic Vibrionaceae.