PKCα Is Recruited to Staphylococcus aureus-Containing Phagosomes and Impairs Bacterial Replication by Inhibition of Autophagy.
PKCα Is Recruited to Staphylococcus aureus-Containing Phagosomes and Impairs Bacterial Replication by Inhibition of Autophagy.
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DOI：
10.3389/fimmu.2021.662987
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发表时间：
2021
影响因子：
7.3
通讯作者：
Colombo MI
中科院分区：
文献类型：
--
作者：
Gauron MC;Newton AC;Colombo MI
劫持自噬机制是侵入性病原体如金黄色葡萄球菌在其宿主细胞中复制的关键机制。我们先前已经证明，细菌在逃逸到细胞质之前，在用自噬蛋白LC 3标记的吞噬体中复制。在这里，我们发现Ca 2+依赖性PKCα与S.金黄色葡萄球菌的吞噬体和分泌的α-溶血素。金黄色葡萄球菌促进PKCα向吞噬体膜的募集。有趣的是，PKCα的存在阻止了自噬蛋白LC 3的结合。使用PKC活性报告基因CKAR的活细胞成像实验表明，用S。含有葡萄球菌分泌因子的金黄色葡萄球菌培养物上清液瞬时激活PKC。功能研究表明，PKCα的过表达导致细菌复制的显著抑制。总之，我们的数据确定增强PKCα活性作为抑制S.在哺乳动物细胞中复制。
Hijacking the autophagic machinery is a key mechanism through which invasive pathogens such as Staphylococcus aureus replicate in their host cells. We have previously demonstrated that the bacteria replicate in phagosomes labeled with the autophagic protein LC3, before escaping to the cytoplasm. Here, we show that the Ca2+-dependent PKCα binds to S. aureus-containing phagosomes and that α-hemolysin, secreted by S. aureus, promotes this recruitment of PKCα to phagosomal membranes. Interestingly, the presence of PKCα prevents the association of the autophagic protein LC3. Live cell imaging experiments using the PKC activity reporter CKAR reveal that treatment of cells with S. aureus culture supernatants containing staphylococcal secreted factors transiently activates PKC. Functional studies reveal that overexpression of PKCα causes a marked inhibition of bacterial replication. Taken together, our data identify enhancing PKCα activity as a potential approach to inhibit S. aureus replication in mammalian cells.
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影响因子：
5.7
作者：
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