Evasion of Toll-like receptor 5 by flagellated bacteria
Evasion of Toll-like receptor 5 by flagellated bacteria
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DOI：
10.1073/pnas.0502040102
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发表时间：
2005-06-28
影响因子：
11.1
通讯作者：
Aderem, A
中科院分区：
文献类型：
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作者：
Andersen-Nissen, E;Smith, KD;Aderem, A
Toll样受体5（TLR5）识别细菌鞭毛蛋白上一个在进化上保守的位点，该位点是鞭毛丝组装和运动所必需的。α和ε变形菌，包括重要的人类病原体空肠弯曲菌、幽门螺杆菌和杆菌状巴尔通体，需要鞭毛运动才能有效地感染哺乳动物宿主。在这项研究中，我们证明这些细菌产生的鞭毛蛋白分子不被TLR5识别。我们将负责逃避TLR5识别的位点定位到N端D1结构域的第89 - 96位氨基酸，该区域位于先前定义的TLR5识别位点的中心位置。沙门氏菌鞭毛蛋白能被TLR5强烈识别，但将第89 - 96位氨基酸突变为相应的幽门螺杆菌flaA序列会消除TLR5的识别，同时也破坏细菌的运动性。为了保持细菌的运动性，α和ε变形菌在鞭毛蛋白分子的其他区域具有补偿性的氨基酸变化，并且我们构建了一种逃避TLR5但保留运动性的沙门氏菌鞭毛蛋白突变体。这些结果表明，逃避TLR5对于这部分细菌在动物黏膜部位的生存至关重要，并提出了一个有趣的可能性，即鞭毛蛋白受体提供了选择性压力，推动了这些独特的细菌鞭毛蛋白亚类的进化。
Toll-like receptor 5 (TLR5) recognizes an evolutionarily conserved site on bacterial flagellin that is required for flagellar filament assembly and motility. The a and E Proteobacteria, including the important human pathogens Campylobacter jejuni, Helicobacter pylori, and Bartonella bacilliformis, require flagellar motility to efficiently infect mammalian hosts. In this study, we demonstrate that these bacteria make flagellin molecules that are not recognized by TLR5. We map the site responsible for TLR5 evasion to amino acids 89-96 of the N-terminal D1 domain, which is centrally positioned within the previously defined TLRS recognition site. Salmonella flagellin is strongly recognized by TLR5, but mutating residues 89-96 to the corresponding H. pylori flaA sequence abolishes TLR5 recognition and also destroys bacterial motility. To preserve bacterial motility, a and E Proteobacteria possess compensatory amino acid changes in other regions of the flagellin molecule, and we engineer a mutant form of Salmonella flagellin that evades TLR5 but retains motility. These results suggest that TLR5 evasion is critical for the survival of this subset of bacteria at mucosal sites in animals and raise the intriguing possibility that flagellin receptors provided the selective force to drive the evolution of these unique subclasses of bacterial flagellins.