Staphylococcus aureus Alpha-Toxin Induces the Formation of Dynamic Tubules Labeled with LC3 within Host Cells in a Rab7 and Rab1b-Dependent Manner.
Staphylococcus aureus Alpha-Toxin Induces the Formation of Dynamic Tubules Labeled with LC3 within Host Cells in a Rab7 and Rab1b-Dependent Manner.
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DOI：
10.3389/fcimb.2017.00431
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发表时间：
2017
影响因子：
5.7
通讯作者：
Colombo MI
中科院分区：
文献类型：
--
作者：
López de Armentia MM;Gauron MC;Colombo MI
金黄色葡萄球菌是一种引起严重传染病的病原体，最终导致败血症和中毒性休克。金黄色葡萄球菌感染的特征是产生毒力因子，包括酶和毒素。内化后，金黄色葡萄球菌驻留在用 Rab7 蛋白标记的吞噬体中。在这里，我们发现金黄色葡萄球菌在感染后早期产生了用小 GTPases Rab1b 和 Rab7 以及自噬蛋白 LC3 标记的管状结构。正如活细胞成像所示，这些管状结构具有高度动态性、延伸、分支和长度增长。我们将它们命名为金黄色葡萄球菌诱导丝 (Saf)。此外，我们证明这些丝的形成取决于微管的完整性以及运动蛋白驱动蛋白-1 (Kif5B) 和 Rab 相互作用溶酶体蛋白 (RILP) 的活性。我们小组之前曾报道，α-溶血素是金黄色葡萄球菌的一种分泌毒素，负责激活细菌诱导的自噬途径。在本报告中，我们证明自噬蛋白 LC3 被招募到金黄色葡萄球菌诱导的细丝膜上，并且 α-溶血素是诱导 Saf 形成的毒素。有趣的是，增加细胞内 cAMP 水平显着抑制 Saf 生物合成。值得注意的是，在这份报告中，我们展示了从含有金黄色葡萄球菌的吞噬体中出现的管状结构的形成，并且这些管状结构的产生似乎是细菌有效复制所必需的。
Staphylococcus aureus is a pathogen that causes severe infectious diseases that eventually lead to septic and toxic shock. S. aureus infection is characterized by the production of virulence factors, including enzymes and toxins. After internalization S. aureus resides in a phagosome labeled with Rab7 protein. Here, we show that S. aureus generates tubular structures marked with the small GTPases Rab1b and Rab7 and by the autophagic protein LC3 at early times post-infection. As shown by live cell imaging these tubular structures are highly dynamic, extend, branch and grow in length. We have named them S. aureus induced filaments (Saf). Furthermore, we demonstrate that the formation of these filaments depends on the integrity of microtubules and the activity of the motor protein Kinesin-1 (Kif5B) and the Rab-interacting lysosomal protein (RILP). Our group has previously reported that α-hemolysin, a secreted toxin of S. aureus, is responsible of the activation of the autophagic pathway induced by the bacteria. In the present report, we demonstrate that the autophagic protein LC3 is recruited to the membrane of S. aureus induced filaments and that α-hemolysin is the toxin that induces Saf formation. Interestingly, increasing the levels of intracellular cAMP significantly inhibited Saf biogenesis. Remarkably in this report we show the formation of tubular structures that emerge from the S. aureus-containing phagosome and that these tubules generation seems to be required for efficient bacteria replication.
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