Cell Biology Program.
Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada.
Autophagy. 2020 Jan;16(1):169-170. doi: 10.1080/15548627.2019.1677322. Epub 2019 Oct 13.
Inhibition of host macroautophagy/autophagy is one of the strategies used by several intracellular pathogens, including , to escape killing. Here we discuss our recent work that revealed the novel mechanism by which the vacuolating cytotoxin A (VacA) produced by inhibits lysosomal and autophagic killing. We discovered that VacA impairs the activity of the lysosomal calcium channel MCOLN1/TRPML1 leading to the formation of enlarged, dysfunctional lysosomes and autophagosomes that serve as an intracellular niche, which allows the bacteria to escape eradication therapy.
宿主巨自噬/自噬的抑制是包括 在内的几种细胞内病原体用来逃避杀伤的策略之一。在这里,我们讨论了我们最近的工作,揭示了由 产生的空泡细胞毒素 A (VacA) 抑制溶酶体和自噬杀伤的新机制。我们发现 VacA 损害溶酶体钙通道 MCOLN1/TRPML1 的活性,导致形成扩大的、功能失调的溶酶体和自噬体,作为一个细胞内小生境,使细菌能够逃避清除治疗。