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The OmpU outer membrane protein, a potential adherence factor of Vibrio cholerae.

机译:OmpU外膜蛋白是霍乱弧菌的潜在粘附因子。

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Expression of the OmpU outer membrane protein of Vibrio cholerae is positively regulated by toxR, which also regulates critical virulence factors such as cholera toxin and the toxin-coregulated pilus colonization factor. In this study, we have characterized the 38-kDa OmpU protein and investigated its role in the adhesion of V. cholerae to mammalian cells. The amino-terminal sequence of OmpU has similarity with the sequences of Haemophilus influenzae HMW1 and HMW2 adhesins, which, in turn, also have similarity with the sequence of Bordetella pertussis filamentous hemagglutinin. A monoclonal antibody directed against FHA recognized both V. cholerae OmpU and Escherichia coli OmpA, and polyclonal anti-OmpU antibodies recognized FHA and E. coli OmpA, suggesting the existence of common epitopes among these proteins. OmpU was strongly recognized by convalescent-phase serum from volunteers experimentally infected with virulent V. cholerae strains, indicating that OmpU is immunogenic and produced in vivo. OmpU selectively bound to fibronectin and to an arginine-glycine-asparagine (RGD) tripeptide but not to other matrix glycoproteins tested such as collagen or laminin. Antibodies directed against OmpU or their F(ab)2 fragments completely inhibited adhesion of several V. cholerae strains to HeLa, HEp-2, Caco-2, and Henle 407 epithelial cells and also inhibited intestinal colonization and conferred protection in newborn mice against both biotypes (El Tor and classical) of V. cholerae O1. Collectively, these data indicate that OmpU has adhesive properties which may play a role in the pathogenesis of cholera.
机译:霍乱弧菌的OmpU外膜蛋白的表达受到toxR的正向调控,它还可以调节关键的毒力因子,例如霍乱毒素和毒素结合的菌毛定殖因子。在这项研究中,我们已经表征了38 kDa OmpU蛋白,并研究了其在霍乱弧菌对哺乳动物细胞的粘附中的作用。 OmpU的氨基末端序列与流感嗜血杆菌HMW1和HMW2黏附素的序列相似,而后者又与百日咳博德特氏菌丝状血凝素的序列相似。针对FHA的单克隆抗体可识别霍乱弧菌OmpU和大肠杆菌OmpA,而多克隆抗OmpU抗体可识别FHA和大肠杆菌OmpA,这表明这些蛋白质中存在共同的表位。 OmpU被恢复期血清中的强力霍乱弧菌菌株实验性感染的志愿者强烈识别,表明OmpU具有免疫原性并在体内产生。 OmpU选择性结合纤连蛋白和精氨酸-甘氨酸-天冬酰胺(RGD)三肽,但不结合其他测试的基质糖蛋白,例如胶原蛋白或层粘连蛋白。针对OmpU的抗体或其F(ab)2片段完全抑制了几种霍乱弧菌菌株与HeLa,HEp-2,Caco-2和Henle 407上皮细胞的粘附,并且还抑制了肠道定植并赋予新生小鼠针对这两种抗体的保护霍乱弧菌O1的生物型(El Tor和经典型)。总的来说,这些数据表明OmpU具有粘附特性,可能在霍乱的发病机理中起作用。

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