The three-dimensional structure of CFA/I adhesion pili: Traveler's diarrhea bacteria hang on by a spring

The three-dimensional structure of CFA/I adhesion pili: Traveler's diarrhea bacteria hang on by a spring
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DOI:
10.1016/j.jmb.2007.10.067
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发表时间:
2008-02-22
影响因子:
5.6
通讯作者:
Bullitt, Esther
Bullitt, Esther
中科院分区:
生物学2区
文献类型:
--
作者:
Mu, Xuang-Qi;Savarino, Stephen J.;Bullitt, Esther

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为了在剧烈搅动的肠道中生存,细菌通过一种叫做皮利(或菌毛)的细纤维附着在宿主的上皮细胞上。表达定植因子抗原I(CFA/I)皮利和相关皮利的肠致病性大肠杆菌是包括旅行者腹泻在内的腹泻病的最常见已知细菌原因。CFA/I皮利通过交替的伴侣蛋白途径组装,对于这些致病菌在小肠的结合和定殖是必需的。在此,我们阐明了CFA/I皮利的独特结构特征,这些结构特征似乎优化了它们作为肠道细菌系链的功能。使用透射电子显微镜的负染色样品结合迭代三维螺旋重建方法进行图像处理,我们确定了CFA/I菌毛丝的结构。我们的研究结果表明,一个坚固的弹簧状螺旋线圈之间的强端对端蛋白质相互作用和弱相互作用提供了维持细菌粘附和诱发肠道疾病所需的强度,稳定性和灵活性的组合。我们认为CFA/I皮利的行为就像一个弹簧,以保持附着在肠粘膜的涡旋混合和向下流动的肠内容物,从而持续足够长的时间,这些细菌定植宿主上皮细胞和引起肠道疾病。(C)2007爱思唯尔有限公司版权所有。
To survive the harsh environment of a churning intestinal tract, bacteria attach to the host epithelium via thin fibers called pili (or fimbriae). Enterotoxigenic Escherichia coli bacteria expressing colonization factor antigen I (CFA/I) pili and related pili are the most common known bacterial cause of diarrheal disease, including traveler's diarrhea. CFA/I pili, assembled via the alternate chaperone pathway, are essential for binding and colonization of the small bowel by these pathogenic bacteria. Herein, we elucidate unique structural features of CFA/I pili that appear to optimize their function as bacterial tethers in the intestinal tract. Using transmission electron microscopy of negatively stained samples in combination with iterative three-dimensional helical reconstruction methods for image processing, we determined the structure of the CFA/I pilus filament. Our results indicate that strong end-to-end protein interactions and weak interactions between the coils of a sturdy spring-like helix provide the combination of strength, stability, and flexibility required to sustain bacterial adhesion and incite intestinal disease. We propose that CFA/I pili behave like a spring to maintain attachment to the gut lining during vortex mixing and downward flow of the intestinal contents, thereby persisting long enough for these bacteria to colonize the host epithelium and cause enteric disease. (C) 2007 Elsevier Ltd. All rights reserved.