Spangler B D
Biological and Medical Research Division, Argonne National Laboratory, Illinois 60439.
Microbiol Rev. 1992 Dec;56(4):622-47. doi: 10.1128/mr.56.4.622-647.1992.
Cholera and the related Escherichia coli-associated diarrheal disease are important problems confronting Third World nations and any area where water supplies can become contaminated. The disease is extremely debilitating and may be fatal in the absence of treatment. Symptoms are caused by the action of cholera toxin, secreted by the bacterium Vibrio cholerae, or by a closely related heat-labile enterotoxin, produced by Escherichia coli, that causes a milder, more common traveler's diarrhea. Both toxins bind receptors in intestinal epithelial cells and insert an enzymatic subunit that modifies a G protein associated with the adenylate cyclase complex. The consequent stimulated production of cyclic AMP, or other factors such as increased synthesis of prostaglandins by intoxicated cells, initiates a metabolic cascade that results in the excessive secretion of fluid and electrolytes characteristic of the disease. The toxins have a very high degree of structural and functional homology and may be evolutionarily related. Several effective new vaccine formulations have been developed and tested, and a growing family of endogenous cofactors is being discovered in eukaryotic cells. The recent elucidation of the three-dimensional structure of the heat-labile enterotoxin has provided an opportunity to examine and compare the correlations between structure and function of the two toxins. This information may improve our understanding of the disease process itself, as well as illuminate the role of the toxin in studies of signal transduction and G-protein function.
霍乱以及与之相关的大肠杆菌所致腹泻病，是第三世界国家以及任何供水可能被污染地区所面临的重要问题。这种疾病极具衰弱性，若不治疗可能会致命。症状是由霍乱弧菌分泌的霍乱毒素，或由大肠杆菌产生的一种密切相关的不耐热肠毒素的作用引起的，后者会导致一种较为轻微、更为常见的旅行者腹泻。两种毒素都能结合肠上皮细胞中的受体，并插入一个酶亚基，该亚基会修饰与腺苷酸环化酶复合物相关的G蛋白。由此导致的环磷酸腺苷（cAMP）的刺激产生，或其他因素，如中毒细胞中前列腺素合成增加等，引发了一个代谢级联反应，导致该病特有的液体和电解质过度分泌。这些毒素在结构和功能上具有高度同源性，可能在进化上相关。已经研发并测试了几种有效的新型疫苗制剂，并且在真核细胞中发现了越来越多的内源性辅因子。最近对不耐热肠毒素三维结构的阐明，为研究和比较这两种毒素的结构与功能之间的相关性提供了契机。这些信息可能会增进我们对疾病过程本身的理解，同时也能阐明毒素在信号转导和G蛋白功能研究中的作用。
