A parallel intraphagosomal survival strategy shared by Mycobacterium tuberculosis and Salmonella enterica
A parallel intraphagosomal survival strategy shared by Mycobacterium tuberculosis and Salmonella enterica
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DOI：
10.1046/j.1365-2958.2000.01797.x
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发表时间：
2000-03-01
影响因子：
3.6
通讯作者：
Groisman, EA
中科院分区：
文献类型：
--
作者：
Buchmeier, N;Blanc-Potard, A;Groisman, EA
结核分枝杆菌和肠道沙门氏菌引起的疾病截然不同，只是远亲关系。然而，巨噬细胞内的生长对这两种细胞内病原体的毒力至关重要。在这里，我们证明，尽管系统发育的距离，结核分枝杆菌和沙门氏菌使用一个平行的生存策略，在巨噬细胞吞噬体内的生长。以前的研究证实，沙门氏菌MGTC基因是巨噬细胞内生长和体内毒力所必需的。结核分枝杆菌含有一个开放阅读框，与沙门氏菌MGTC蛋白有38%的氨基酸同源性。MGTC灭活后，结核分枝杆菌突变株对培养的人巨噬细胞的毒力减弱，对小鼠肺和脾的生长也造成损害。MGTC突变体的复制在体外被低镁和中等酸性pH的组合所抑制，这表明含有结核分枝杆菌的吞噬小体具有这些特征。结核分枝杆菌和沙门氏菌的MGTC突变体所表现出的相似表型表明，获得镁的能力对于在巨噬细胞吞噬体内增殖的细胞内病原体的毒力是必不可少的。
Mycobacterium tuberculosis and Salmonella enterica cause very different diseases and are only distantly related. However, growth within macrophages is crucial for virulence in both of these intracellular pathogens. Here, we demonstrate that in spite of the phylogenetic distance, M. tuberculosis and Salmonella employ a parallel survival strategy for growth within macrophage phagosomes. Previous studies established that the Salmonella mgtC gene is required for growth within macrophages and for virulence in vivo. M. tuberculosis contains an open reading frame exhibiting 38% amino acid identity with the Salmonella MgtC protein. Upon inactivation of mgtC, the resulting M. tuberculosis mutant was attenuated for virulence in cultured human macrophages and impaired for growth in the lungs and spleens of mice. Replication of the mgtC mutant was inhibited in vitro by a combination of low magnesium and mildly acidic pH suggesting that the M. tuberculosis-containing phagosome has these characteristics. The similar phenotypes displayed by the mgtC mutants of M. tuberculosis and Salmonella suggest that the ability to acquire magnesium is essential for virulence in intracellular pathogens that proliferate within macrophage phagosomes.