Zitzer A, Wassenaar T M, Walev I, Bhakdi S
Institute for Medical Microbiology, Johannes Gutenberg University, Mainz, Germany.
Infect Immun. 1997 Apr;65(4):1293-8. doi: 10.1128/iai.65.4.1293-1298.1997.
Many strains of Vibrio cholerae non-O1 and O1 El Tor that cause diarrhea do not harbor genes for a known secretogenic toxin. However, these strains usually elaborate a pore-forming toxin, hitherto characterized as a hemolysin and here designated V. cholerae cytolysin, whose action on intestinal cells has not yet been described. We report that V. cholerae cytolysin binds as a monomer to Intestine 407 cells and then assembles into detergent-stable oligomers that probably represent tetra- or pentamers. Oligomer formation is accompanied by generation of small transmembrane pores that allow rapid flux of K+ but not influx of Ca2+ or propidium iodide. Pore formation is followed by irreversible ATP depletion and cell death. Binding of fewer than 10(4) toxin molecules per cell in vitro is lethal. The possibility is raised that production of this toxin by bacteria that are in close contact with intestinal cells is rapidly cytocidal in vivo, and death of intestinal cells may be a cause of diarrhea.
许多引起腹泻的非O1群霍乱弧菌和O1群埃尔托生物型霍乱弧菌菌株并不携带已知的分泌毒素基因。然而，这些菌株通常会产生一种成孔毒素，此前被鉴定为溶血素，在此命名为霍乱弧菌溶细胞素，其对肠道细胞的作用尚未见报道。我们报告霍乱弧菌溶细胞素以单体形式与肠407细胞结合，然后组装成去污剂稳定的寡聚体，可能是四聚体或五聚体。寡聚体形成伴随着小跨膜孔的产生，这些孔允许K+快速通透，但不允许Ca2+或碘化丙啶内流。孔形成后会导致不可逆的ATP消耗和细胞死亡。体外每个细胞结合少于10^4个毒素分子就具有致死性。这就提出了一种可能性，即与肠道细胞紧密接触的细菌产生的这种毒素在体内能迅速导致细胞死亡，而肠道细胞死亡可能是腹泻的一个原因。
