Open AccessA tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion
Author(s) -
Aftab Nadeem,
Raghavendra Sashi Krishgampalli,
Eric Toh,
Athar Alam,
Si Lhyam Myint,
T.V. Heidler,
Mitesh Dongre,
Nikola Zlatkov,
Hudson Pace,
Fouzia Bano,
Anders Sjöstedt,
Marta Bally,
Bernt Eric Uhlin,
Sun Nyunt Wai,
Karina Persson
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2111418118
Subject(s) - vibrio cholerae , biology , caenorhabditis elegans , microbiology and biotechnology , cholera toxin , flagellum , escherichia coli , secretion , toxin , cytolysis , virulence , mutant , biochemistry , gene , cytotoxicity , bacteria , in vitro , genetics
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 threeV. 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 theV. 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.