Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection
Role of flagella in pathogenesis of Pseudomonas aeruginosa pulmonary infection
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DOI：
10.1128/iai.66.1.43-51.1998
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发表时间：
1998-01-01
影响因子：
3.1
通讯作者：
Prince, A
中科院分区：
文献类型：
--
作者：
Feldman, M;Bryan, R;Prince, A
铜绿假单胞菌菌株是机会性病原体，与免疫功能低下的宿主以及囊性纤维化患者的感染有关。像许多其他黏膜病原体一样，铜绿假单胞菌细胞表达鞭毛，鞭毛提供运动性和趋向优选底物的趋化性，但也为吞噬细胞的清除提供了一个配体。我们通过在新生小鼠肺炎模型中比较fliC突变体的毒力，测试了鞭毛在呼吸道感染初始阶段的作用。在缺乏fliC的情况下，没有死亡发生，相比之下，亲本菌株PAK导致30%的死亡率，而pilA突变体PAK/NP相关的感染导致15%的死亡率（P < 0.0001）。无论菌毛是否表达，fliC突变体仅在25%接种的小鼠中引起肺炎，而亲本菌株与80%的肺炎发生率相关。组织病理学研究表明，fliC突变体引起非常局灶性的炎症，并且该菌不像PAK或PAK/NP感染时那样在肺部扩散。纯化的鞭毛蛋白在小鼠肺部引起强烈的炎症反应。在体外结合试验中，I - 125标记的鞭毛蛋白与糖脂GM1和GD(1a)以及无唾液酸GM1结合。然而，鞭毛蛋白介导的与上皮神经节苷脂的结合是一个相对不常见的事件，这通过野生型或fliC突变体生物体与含有膜结合GM1的CHO Lec - 2细胞的结合试验进行了量化。Fla(+)生物体（而不是fliC突变体）能被小鼠巨噬细胞有效摄取。铜绿假单胞菌的鞭毛在呼吸道感染的建立中很重要，并且可能在与上皮细胞膜的初始相互作用中起到一种束缚作用。这种功能被鞭毛对宿主清除机制的贡献所抵消，这些机制促进吞噬清除以及鞭毛基因在黏蛋白结合和清除中的作用。
Pseudomonas aeruginosa strains are opportunistic pathogens associated with infections in immunocompromised hosts and patients with cystic fibrosis, Like many other mucosal pathogens, P. aeruginosa cells express flagella which provide motility and chemotaxis toward preferred substrates but also provide a ligand for clearance by phagocytic cells. We tested the role of flagella in the initial stages of respiratory tract infection by comparing the virulence of fliC mutants in a neonatal mouse model of pneumonia. In the absence of fliC, there was no mortality, compared with 30% mortality attributed to the parental strain PAK or 15% mortality associated with infection due to a pilA mutant PAK/NP (P < 0.0001). The fliC mutants caused pneumonia in only 25% of the mice inoculated, regardless of whether there was expression of the pilus, whereas the parental strain was associated with an 80% rate of pneumonia. Histopathological studies demonstrated that the fliC mutants caused very focal inflammation and that the organisms did not spread through the lungs as seen in infection due to either PAK or PAK/NP. Purified flagellin elicited an intense inflammatory response in the mouse lung. I-125-labeled flagellin bound to the glycolipids GM1 and GD(1a) and to asialoGM1 in an in vitro binding assay. However, flagellin-mediated binding to epithelial gangliosides was a relatively unusual event, as quantified by binding assays of wild-type or fliC mutant organisms to CHO Lec-2 cells with membrane-incorporated GM1. Fla(+) organisms but not fliC mutants were efficiently taken up by murine macrophages. P. aeruginosa flagella are important in the establishment of respiratory tract infection and may act as a tether in initial interactions with epithelial membranes. This function is offset by the contribution of flagella to host clearance mechanisms facilitating phagocytic clearance and the role of flagellar genes in mucin binding and clearance.