Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli
Structure of CFA/I fimbriae from enterotoxigenic Escherichia coli
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DOI：
10.1073/pnas.0812843106
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发表时间：
2009-06-30
影响因子：
11.1
通讯作者：
Bullitt, Esther
中科院分区：
文献类型：
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作者：
Li, Yong-Fu;Poole, Steven;Bullitt, Esther
粘附皮利在引起肠致病性大肠杆菌（ETEC）肠道定植和肠道疾病的过程中起重要作用。大肠杆菌致病型，造成巨大的全球疾病负担。我们阐明原子结构的ETEC主要菌毛蛋白亚基，CfaB，从定植因子抗原I（CFA/I）菌毛。这些数据被用来构建模型的CFA/I菌毛，都是在体内观察到的2种形态学形式：它通常组装成的螺旋丝，和一个扩展的，未缠绕的构象。建模和确证的突变数据表明，脯氨酸异构化参与这些螺旋和扩展形式之间的转换。我们的研究结果证实了5类菌毛（来自主要引起胃肠道疾病的细菌）和1类皮利（来自引起泌尿道、呼吸道和其他感染的细菌）之间在缺乏显著的一级序列相似性的情况下所观察到的强烈的结构相似性。他们还表明，菌毛类型之间的形态和生化差异，无论类别如何，提供结构特化，促进每种细菌致病型在其首选宿主微环境中的存活。最后，我们提出了细菌利用抗原变异来逃避宿主免疫反应的结构证据，其中占据CfaB和相关5类菌毛蛋白的预测表面暴露面的残基显示出比菌毛蛋白的其余部分高得多的遗传序列变异性。
Adhesion pili (fimbriae) play a critical role in initiating the events that lead to intestinal colonization and diarrheal disease by enterotoxigenic Escherichia coli (ETEC), an E. coli pathotype that inflicts an enormous global disease burden. We elucidate atomic structures of an ETEC major pilin subunit, CfaB, from colonization factor antigen I (CFA/I) fimbriae. These data are used to construct models for 2 morphological forms of CFA/I fimbriae that are both observed in vivo: the helical filament into which it is typically assembled, and an extended, unwound conformation. Modeling and corroborative mutational data indicate that proline isomerization is involved in the conversion between these helical and extended forms. Our findings affirm the strong structural similarities seen between class 5 fimbriae (from bacteria primarily causing gastrointestinal disease) and class 1 pili (from bacteria that cause urinary, respiratory, and other infections) in the absence of significant primary sequence similarity. They also suggest that morphological and biochemical differences between fimbrial types, regardless of class, provide structural specialization that facilitates survival of each bacterial pathotype in its preferred host microenvironment. Last, we present structural evidence for bacterial use of antigenic variation to evade host immune responses, in that residues occupying the predicted surface-exposed face of CfaB and related class 5 pilins show much higher genetic sequence variability than the remainder of the pilin protein.