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In vivo covalent cross‐linking of cellular actin by the Vibrio cholerae RTX toxin
Author(s) -
Fullner Karla Jean,
Mekalanos John J.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.20.5315
Subject(s) - vibrio cholerae , biology , toxin , microbiology and biotechnology , in vivo , cholera toxin , actin , vibrionaceae , bacteria , genetics
Enteric pathogens often export toxins that elicit diarrhea as a part of the etiology of disease, including toxins that affect cytoskeletal structure. Recently, we discovered that the intestinal pathogen Vibrio cholerae elicits rounding of epithelial cells that is dependent upon a gene we designated rtxA . Here we investigate the association of rtxA with the cell‐rounding effect. We find that V.cholerae exports a large toxin, RTX (repeats‐in‐toxin) toxin, to culture supernatant fluids and that this toxin is responsible for cell rounding. Furthermore, we find that cell rounding is not due to necrosis, suggesting that RTX toxin is not a typical member of the RTX family of pore‐forming toxins. Rather, RTX toxin causes depolymerization of actin stress fibers and covalent cross‐linking of cellular actin into dimers, trimers and higher multimers. This RTX toxin‐specific cross‐linking occurs in cells previously rounded with cytochalasin D, indicating that G‐actin is the toxin target. Although several models explain our observations, our simultaneous detection of actin cross‐linking and depolymerization points toward a novel mechanism of action for RTX toxin, distinguishing it from all other known toxins.