Division of Infectious Disease and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Nat Commun. 2022 Jun 27;13(1):3656. doi: 10.1038/s41467-022-31351-y.
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.
斑点热群立克次体是节肢动物传播的专性细胞内细菌，可引起轻度至重度人类疾病。这些细菌侵入宿主细胞，在细胞质中复制，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逃避膜结合的空泡。在这里，我们表明，一种类脂酶 A2 酶（Pat1）通过促进从宿主膜逃逸和细胞间传播来促进帕克立克次体感染。Pat1 对小鼠模型中的感染很重要，在细胞水平上，它对于从单层和双层膜结合的空泡有效地逃逸到宿主细胞质中以及避免标记受损膜的宿主半乳糖凝集素至关重要。Pat1 对于避免宿主多泛素化、防止自噬受体 p62 的募集以及促进肌动蛋白依赖的运动和细胞间传播也很重要。
