Deletion of the β-Propeller Protein Gene Rv1057 Reduces ESAT-6 Secretion and Intracellular Growth of Mycobacterium tuberculosis
Deletion of the β-Propeller Protein Gene Rv1057 Reduces ESAT-6 Secretion and Intracellular Growth of Mycobacterium tuberculosis
复制标题
β-螺旋桨蛋白基因 Rv1057 的缺失会减少结核分枝杆菌的 ESAT-6 分泌和细胞内生长。
DOI：
10.1007/s00284-017-1394-8
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发表时间：
2018-04-01
影响因子：
2.6
通讯作者：
Cao, Guangxiang
中科院分区：
文献类型：
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作者：
Fu, Jiafang;Zong, Gongli;Cao, Guangxiang
Rv 1057是结核分枝杆菌中唯一的β-螺旋桨蛋白，但其生物学功能尚不清楚。在本研究中，我们在致病性M.结核菌株H37 Rv，并检查了体外和巨噬细胞中的突变体的特征。我们发现Rv 1057的缺失减少了主要毒力因子ESAT-6的分泌，并且ESAT-6在分泌期间停止在细胞包膜部分中，尽管ESAT-6水平在突变株和对照株的裂解物中相似。在感染的巨噬细胞中，Rv 1057缺失显著降低了细胞因子IL-1 β、IL-10、TNF-α和INF-γ的分泌水平，但不影响IL-4和IL-8。D1057感染的巨噬细胞也比H37 Rv和D1057 com（D1057 com的Rv 1057补充菌株）感染的巨噬细胞释放更少的LDH并产生更多的一氧化氮（NO），表明D1057与H37 Rv或D1057 com相比具有降低的细胞毒性。此外，Rv 1057缺失突变体在巨噬细胞中生长的能力显著低于H37 Rv和D1057 com。我们的研究结果支持Rv 1057在ESAT-6分泌和调节M.结核和巨噬细胞。
Rv1057 is the only beta-propeller protein in Mycobacterium tuberculosis, but its biological function is still unclear. In this study, we generated a deletion mutant of Rv1057 (D1057) in the virulent M. tuberculosis strain H37Rv and examined the characteristics of the mutant in vitro and in macrophages. We found that deletion of Rv1057 reduces secretion of the major virulence factor ESAT-6 and ESAT-6 stops in the cell envelope fraction during secretion, although ESAT-6 levels were similar in lysates of the mutant and control strains. In infected macrophages, Rv1057 deletion significantly reduced the secretion levels of cytokines IL-1 beta, IL-10, TNF-alpha, and INF-gamma, but did not affect IL-4 and IL-8. D1057-infected macrophages also release less LDH and produce more nitric oxide (NO) than H37Rv- and D1057com (Rv1057 complemented strain of D1057com)-infected macrophages, indicating that D1057 has the decreased cytotoxicity compared to H37Rv or D1057com. In addition, the capacity of the Rv1057 deletion mutant to grow in macrophages was significantly lower than that of H37Rv and D1057com. Our findings support a role for Rv1057 in ESAT-6 secretion and in modulating the interactions between M. tuberculosis and macrophages.