Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family

Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family
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DOI:
10.1126/science.288.5470.1436
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发表时间:
2000-05-26
期刊:
影响因子:
56.9
通讯作者:
Falkow, S
Falkow, S
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Ramakrishnan, L;Federspiel, NA;Falkow, S

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致病分枝杆菌,包括结核病的病原体,必须在巨噬细胞中复制,以便在慢性感染期间在其利基内长期存活:有组织的巨噬细胞和淋巴细胞集合,称为肉芽肿。我们鉴定出几个基因在引起鱼类和两栖类结核病的海洋分枝杆菌中优先表达。存在于宿主肉芽肿和/或巨噬细胞中。两个是结核分枝杆菌PE/PE-PGRs基因的同源物,这个家族编码大量重复的富含甘氨酸的蛋白,功能未知。两个PE-PGRS基因的突变导致海洋分枝杆菌不能在巨噬细胞中复制,并在肉芽肿中持久性降低。我们的结果建立了一些PE-PGRS蛋白的毒力的直接作用。
Pathogenic mycobacteria, including the agent of tuberculosis, Mycobacterium tuberculosis, must replicate in macrophages for long-term persistence within their niche during chronic infection: organized collections of macrophages and lymphocytes called granulomas. We identified several genes preferentially expressed when Mycobacterium marinum, the cause of fish and amphibian tuberculosis. resides in host granulomas and/or macrophages. Two were homologs of M. tuberculosis PE/PE-PGRS genes, a family encoding numerous repetitive glycine-rich proteins of unknown function. Mutation of two PE-PGRS genes produced M. marinum strains incapable of replication in macrophages and with decreased persistence in granulomas. Our results establish a direct role in virulence for some PE-PGRS proteins.