Fullner K J, Mekalanos J J
Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, D1-408, Boston, MA 02115, USA.
EMBO J. 2000 Oct 16;19(20):5315-23. doi: 10.1093/emboj/19.20.5315.
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.
肠道病原体通常会分泌毒素，这些毒素会引发腹泻，成为疾病病因的一部分，包括影响细胞骨架结构的毒素。最近，我们发现肠道病原体霍乱弧菌会引发上皮细胞变圆，这依赖于我们命名为rtxA的基因。在此，我们研究rtxA与细胞变圆效应之间的关联。我们发现霍乱弧菌会将一种大型毒素RTX（毒素重复序列）分泌到培养上清液中，且这种毒素是导致细胞变圆的原因。此外，我们发现细胞变圆并非由坏死引起，这表明RTX毒素并非成孔毒素RTX家族的典型成员。相反，RTX毒素会导致肌动蛋白应激纤维解聚，并使细胞内的肌动蛋白共价交联形成二聚体、三聚体及更高阶的多聚体。这种RTX毒素特异性交联发生在先前用细胞松弛素D处理变圆的细胞中，表明G-肌动蛋白是毒素的作用靶点。尽管有几种模型可以解释我们的观察结果，但我们同时检测到的肌动蛋白交联和解聚指向了RTX毒素一种全新的作用机制，使其有别于所有其他已知毒素。
