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Dual Pili Post-translational Modifications Synergize to Mediate Meningococcal Adherence to Platelet Activating Factor Receptor on Human Airway Cells

机译:双重菌毛翻译后修饰协同作用介导脑膜炎球菌对人气道细胞血小板活化因子受体的粘附。

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摘要

Pili of pathogenic Neisseria are major virulence factors associated with adhesion, twitching motility, auto-aggregation, and DNA transformation. Pili of N. meningitidis are subject to several different post-translational modifications. Among these pilin modifications, the presence of phosphorylcholine (ChoP) and a glycan on the pilin protein are phase-variable (subject to high frequency, reversible on/off switching of expression). In this study we report the location of two ChoP modifications on the C-terminus of N. meningitidis pilin. We show that the surface accessibility of ChoP on pili is affected by phase variable changes to the structure of the pilin-linked glycan. We identify for the first time that the platelet activating factor receptor (PAFr) is a key, early event receptor for meningococcal adherence to human bronchial epithelial cells and tissue, and that synergy between the pilin-linked glycan and ChoP post-translational modifications is required for pili to optimally engage PAFr to mediate adherence to human airway cells.
机译:致病性奈瑟氏菌的菌毛是与附着力,抽搐运动性,自动聚集和DNA转化相关的主要毒力因子。脑膜炎奈瑟氏菌的菌毛受到几种不同的翻译后修饰。在这些菌毛蛋白修饰中,菌毛蛋白上磷酸胆碱(ChoP)和聚糖的存在是相变的(受高频,可逆的表达开/关控制)。在这项研究中,我们报告了两个脑膜炎奈瑟菌棉菌素C末端的ChoP修饰的位置。我们表明,ChoP在菌毛上的表面可及性受到菌毛素连接的聚糖结构的相变变化的影响。我们首次确定血小板活化因子受体(PAFr)是脑膜炎球菌对人支气管上皮细胞和组织粘附的关键,早期事件受体,并且菌毛蛋白连接的聚糖和ChoP翻译后修饰之间需要协同作用使菌毛最佳地与PAFr结合以介导对人气道细胞的粘附。

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