A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes.

A patatin-like phospholipase mediates Rickettsia parkeri escape from host membranes.
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DOI:
10.1038/s41467-022-31351-y
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发表时间:
2022-06-27
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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斑点热组的立克次体是节肢动物传播的专性细胞内细菌,可导致轻微到严重的人类疾病。这些细菌侵入宿主细胞,在细胞胞浆中复制,并在细胞间传播。为了进入宿主细胞质并避免免疫检测,它们通过表达破坏宿主膜的因子来避开膜结合的空泡。在这里,我们展示了一种类似Patatin的磷脂酶A2酶(Pat1)通过促进逃避宿主膜和细胞-细胞扩散来促进帕氏立克次体感染。Pat1对于小鼠模型中的感染是重要的,在细胞水平上,对于有效地从单膜和双膜结合的空泡逃脱到宿主胞浆中,以及对于避免标记受损膜的宿主Galectins来说,Pat1是至关重要的。Pat1对于避免宿主多泛素,阻止自噬受体p62的募集,以及促进基于肌动蛋白的运动和细胞-细胞扩散也是重要的。致病立克次体是由节肢动物传播的专性细胞内细菌,它们入侵宿主细胞,在细胞胞浆中复制,并在细胞之间传播。这里,Borgo等人。确定一种对感染重要的立克次体磷脂酶,帮助细菌从宿主细胞空泡逃脱到宿主细胞质中,防止自噬靶向,促进细菌运动并传播到其他细胞。
Rickettsia species of the spotted fever group are arthropod-borne obligate intracellular bacteria that can cause mild to severe human disease. These bacteria invade host cells, replicate in the cell cytosol, and spread from cell to cell. To access the host cytosol and avoid immune detection, they escape membrane-bound vacuoles by expressing factors that disrupt host membranes. Here, we show that a patatin-like phospholipase A2 enzyme (Pat1) facilitates Rickettsia parkeri infection by promoting escape from host membranes and cell-cell spread. Pat1 is important for infection in a mouse model and, at the cellular level, is crucial for efficiently escaping from single and double membrane-bound vacuoles into the host cytosol, and for avoiding host galectins that mark damaged membranes. Pat1 is also important for avoiding host polyubiquitin, preventing recruitment of autophagy receptor p62, and promoting actin-based motility and cell-cell spread. Pathogenic Rickettsia species are arthropod-borne, obligate intracellular bacteria that invade host cells, replicate in the cell cytosol, and spread from cell to cell. Here, Borgo et al. identify a Rickettsia phospholipase enzyme that is important for infection by helping the bacteria escape from host cell vacuoles into the host cytosol, preventing targeting by autophagy, and promoting bacterial motility and spread to other cells.
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