Mycobacterial escape from macrophage phagosomes to the cytoplasm represents an alternate adaptation mechanism.
Mycobacterial escape from macrophage phagosomes to the cytoplasm represents an alternate adaptation mechanism.
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DOI：
10.1038/srep23089
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发表时间：
2016-03-16
影响因子：
4.6
通讯作者：
Rao KV
中科院分区：
文献类型：
--
作者：
Jamwal SV;Mehrotra P;Singh A;Siddiqui Z;Basu A;Rao KV
结核分枝杆菌（Mtb）在宿主巨噬细胞内的存活是通过病原体依赖的吞噬体-溶酶体融合抑制介导的，这使得细菌能够在未成熟的吞噬体腔室中持续存在。通过对不同领域分离株的超微结构检查和生化分析，我们发现一些结核分枝杆菌菌株实际上不适合在感染巨噬细胞的内吞囊泡中生存。相反，通过激活宿主细胞质磷脂酶A2的机制，这些细菌迅速逃离吞噬体，并在宿主细胞的细胞质中建立住所。有趣的是，通过促进对宿主细胞自噬的增强抑制，这种易位充当了另一种毒力获取机制。因此，我们的研究揭示了结核分枝杆菌在宿主巨噬细胞中生存所采用的适应策略的可塑性。
Survival of Mycobacterium tuberculosis (Mtb) within the host macrophage is mediated through pathogen-dependent inhibition of phagosome-lysosome fusion, which enables bacteria to persist within the immature phagosomal compartment. By employing ultrastructural examination of different field isolates supported by biochemical analysis, we found that some of the Mtb strains were in fact poorly adapted for subsistence within endocytic vesicles of infected macrophages. Instead, through a mechanism involving activation of host cytosolic phospholipase A2, these bacteria rapidly escaped from phagosomes, and established residence in the cytoplasm of the host cell. Interestingly, by facilitating an enhanced suppression of host cellular autophagy, this translocation served as an alternate virulence acquisition mechanism. Thus, our studies reveal plasticity in the adaptation strategies employed by Mtb, for survival in the host macrophage.