Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
Infect Immun. 2012 Oct;80(10):3490-500. doi: 10.1128/IAI.00434-12. Epub 2012 Jul 30.
Yersinia pestis and many other Gram-negative pathogenic bacteria use the chaperone/usher (CU) pathway to assemble virulence-associated surface fibers termed pili or fimbriae. Y. pestis has two well-characterized CU pathways: the caf genes coding for the F1 capsule and the psa genes coding for the pH 6 antigen. The Y. pestis genome contains additional CU pathways that are capable of assembling pilus fibers, but the roles of these pathways in the pathogenesis of plague are not understood. We constructed deletion mutations in the usher genes for six of the additional Y. pestis CU pathways. The wild-type (WT) and usher deletion strains were compared in the murine bubonic (subcutaneous) and pneumonic (intranasal) plague infection models. Y. pestis strains containing deletions in CU pathways y0348-0352, y1858-1862, and y1869-1873 were attenuated for virulence compared to the WT strain by the intranasal, but not subcutaneous, routes of infection, suggesting specific roles for these pathways during pneumonic plague. We examined binding of the Y. pestis WT and usher deletion strains to A549 human lung epithelial cells, HEp-2 human cervical epithelial cells, and primary human and murine macrophages. Y. pestis CU pathways y0348-0352 and y1858-1862 were found to contribute to adhesion to all host cells tested, whereas pathway y1869-1873 was specific for binding to macrophages. The correlation between the virulence attenuation and host cell binding phenotypes of the usher deletion mutants identifies three of the additional CU pathways of Y. pestis as mediating interactions with host cells that are important for the pathogenesis of plague.
鼠疫耶尔森氏菌(Yersinia pestis)和许多其他革兰氏阴性致病菌利用伴侣蛋白/usher (CU)途径组装称为菌毛或纤毛的毒力相关表面纤维。鼠疫耶尔森氏菌有两种特征明确的 CU 途径：编码 F1 荚膜的 caf 基因和编码 pH6 抗原的 psa 基因。鼠疫耶尔森氏菌基因组还包含其他能够组装菌毛纤维的 CU 途径，但这些途径在鼠疫发病机制中的作用尚不清楚。我们构建了六个额外的鼠疫耶尔森氏菌 CU 途径的 usher 基因缺失突变。在小鼠败血性（皮下）和肺鼠疫（鼻内）感染模型中比较了野生型（WT）和 usher 缺失菌株。与 WT 菌株相比，含有 CU 途径 y0348-0352、y1858-1862 和 y1869-1873 缺失的鼠疫耶尔森氏菌菌株在鼻内感染途径下的毒力减弱，但在皮下感染途径下没有减弱，这表明这些途径在肺鼠疫中具有特定作用。我们检查了鼠疫耶尔森氏菌 WT 和 usher 缺失菌株与 A549 人肺上皮细胞、HEp-2 人宫颈上皮细胞以及原代人和鼠源巨噬细胞的结合。发现鼠疫耶尔森氏菌 CU 途径 y0348-0352 和 y1858-1862 有助于与所有测试的宿主细胞的粘附，而途径 y1869-1873 则特异性结合巨噬细胞。usher 缺失突变体的毒力衰减和宿主细胞结合表型之间的相关性表明，鼠疫耶尔森氏菌的三个额外 CU 途径作为介导与宿主细胞相互作用的重要途径，这对于鼠疫的发病机制很重要。
