Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy
Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy
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DOI：
10.1073/pnas.0700036104
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发表时间：
2007-04-03
影响因子：
11.1
通讯作者：
Purdy, Georgiana E.
中科院分区：
文献类型：
--
作者：
Alonso, Sylvie;Pethe, Kevin;Purdy, Georgiana E.
结核分枝杆菌寄生于休眠的巨噬细胞，但通过氧化和非氧化机制被活化的巨噬细胞杀死。非氧化机制与含菌吞噬体成熟为酸化的水解活性区室有关。我们在这里描述了一种通过泛素水解产生的肽的活性杀死溶酶体区室中分枝杆菌的机制。在感染的巨噬细胞中诱导自噬增强了泛素缀合物向溶酶体的递送，并增加了溶酶体可溶性组分的杀菌能力。泛素化蛋白在自噬溶酶体中的积累提供了一种可能的机制，这种机制是在自噬宿主细胞中观察到的一系列病原体的抗微生物活性背后的机制。
Mycobacterium tuberculosis parasitizes resting macrophages yet is killed by activated macrophages through both oxidative and nonoxidative mechanisms. Nonoxidative mechanisms are linked to the maturation of the bacteria-containing phagosome into an acidified, hydrolytically active compartment. We describe here a mechanism for killing Mycobacteria in the lysosomal compartment through the activity of peptides generated by the hydrolysis of ubiquitin. The induction of autophagy in infected macrophages enhanced the delivery of ubiquitin conjugates to the lysosome and increased the bactericidal capacity of the lysosomal soluble fraction. The accumulation of ubiquitinated proteins in the autophagolysosome provides one possible mechanism behind the antimicrobial activities observed for a range of pathogens in autophagous host cells.