Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells.
Enterotoxigenic Escherichia coli EtpA mediates adhesion between flagella and host cells.
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DOI：
10.1038/nature07568
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发表时间：
2009-01-29
期刊：
影响因子：
64.8
通讯作者：
Fleckenstein, James M.
中科院分区：
文献类型：
--
作者：
Roy, Koushik;Hilliard, George M.;Hamilton, David J.;Luo, Jiwen;Ostmann, Marguerite M.;Fleckenstein, James M.
对许多革兰氏阴性病原体来说，黏附上皮细胞和鞭毛介导的运动性是关键的毒力特征，包括产肠毒素大肠杆菌(ETEC)，这是发展中国家旅行者和儿童腹泻的主要原因。许多有鞭毛的病原体输出推测的粘附素，属于双伙伴分泌(TPS)家族。然而，这些粘附素的实际功能在很大程度上仍未确定。在这里，我们证明了EtpA，一种产肠毒素大肠杆菌的TPS外蛋白粘附素，模拟并与鞭毛主要亚单位鞭毛蛋白的高度保守区域相互作用，这些相互作用对粘连和肠道定植至关重要。虽然鞭毛蛋白的保守区大多埋在鞭毛柄中，但我们的结果表明，它们至少暂时暴露在鞭毛的顶端，在那里它们捕获EtpA粘附素分子，呈递给真核受体。EtpA与其他运动性病原体编码的分子的相似性表明了细菌黏附的潜在共同范式，而鞭毛蛋白保守区参与黏附对革兰氏阴性病原体疫苗的开发具有重要意义。
Adhesion to epithelial cells and flagella-mediated motility are critical virulence traits for many Gram-negative pathogens, including enterotoxigenic Escherichia coli (ETEC), a major cause of diarrhoea in travellers and children in developing countries. Many flagellated pathogens export putative adhesins belonging to the two-partner secretion (TPS) family. However, the actual function of these adhesins remains largely undefined. Here we demonstrate that EtpA, a TPS exoprotein adhesin of enterotoxigenic Escherichia coli, mimics and interacts with highly conserved regions of flagellin, the major subunit of flagella, and that these interactions are critical for adherence and intestinal colonization. Although conserved regions of flagellin are mostly buried in the flagellar shaft, our results suggest that they are at least transiently exposed at the tips of flagella where they capture EtpA adhesin molecules for presentation to eukaryotic receptors. Similarity of EtpA to molecules encoded by other motile pathogens suggests a potential common paradigm for bacterial adhesion, while participation of conserved regions of flagellin in adherence has implications for development of vaccines for Gram-negative pathogens.
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