Cotter P A, Yuk M H, Mattoo S, Akerley B J, Boschwitz J, Relman D A, Miller J F
Department of Microbiology and Immunology, UCLA School of Medicine, University of California, Los Angeles, California 90095, USA.
Infect Immun. 1998 Dec;66(12):5921-9. doi: 10.1128/IAI.66.12.5921-5929.1998.
Adherence to ciliated respiratory epithelial cells is considered a critical early step in Bordetella pathogenesis. For Bordetella pertussis, the etiologic agent of whooping cough, several factors have been shown to mediate adherence to cells and cell lines in vitro. These putative adhesins include filamentous hemagglutinin (FHA), fimbriae, pertactin, and pertussis toxin. Determining the precise roles of each of these factors in vivo, however, has been difficult, due in part to the lack of natural-host animal models for use with B. pertussis. Using the closely related species Bordetella bronchiseptica, and by constructing both deletion mutation and ectopic expression mutants, we have shown that FHA is both necessary and sufficient for mediating adherence to a rat lung epithelial (L2) cell line. Using a rat model of respiratory infection, we have shown that FHA is absolutely required, but not sufficient, for tracheal colonization in healthy, unanesthetized animals. FHA was not required for initial tracheal colonization in anesthetized animals, however, suggesting that its role in establishment may be dedicated to overcoming the clearance action of the mucociliary escalator.
黏附于呼吸道纤毛上皮细胞被认为是博德特氏菌发病机制中的关键早期步骤。对于百日咳的病原体百日咳博德特氏菌,已有多项研究表明,多种因素可介导其在体外黏附于细胞和细胞系。这些假定的黏附素包括丝状血凝素(FHA)、菌毛、百日咳黏附素和百日咳毒素。然而,要确定这些因素在体内的确切作用一直很困难,部分原因是缺乏用于研究百日咳博德特氏菌的天然宿主动物模型。利用密切相关的支气管败血博德特氏菌,并构建缺失突变体和异位表达突变体,我们发现FHA对于介导黏附大鼠肺上皮(L2)细胞系既是必需的也是充分的。利用大鼠呼吸道感染模型,我们发现FHA对于健康、未麻醉动物的气管定植是绝对必需的,但并不充分。然而,FHA对于麻醉动物的初始气管定植并非必需,这表明其在定植过程中的作用可能是专门用于克服黏液纤毛清除作用。