生物
自噬
沙门氏菌
细胞生物学
TFEB
液泡
效应器
细胞内寄生虫
溶酶体
PI3K/AKT/mTOR通路
生物发生
微生物学
细胞内
细胞质
信号转导
遗传学
基因
细菌
生物化学
酶
细胞凋亡
作者
Ritika Chatterjee,Debalina Chaudhuri,Subba Rao Gangi Setty,Dipshikha Chakravortty
标识
DOI:10.1016/j.micinf.2023.105128
摘要
Salmonella, a stealthy facultative intracellular pathogen, utilises an array of host immune evasion strategies. This facilitates successful survival via replicative niche establishment in otherwise hostile environments such as macrophages. Salmonella survives in and utilises macrophages for effective dissemination, ultimately leading to systemic infection. Bacterial xenophagy or macro-autophagy is an important host defense mechanism in macrophages. Here, we report for the first time that the Salmonella pathogenicity island-1 (SPI-1) effector SopB is involved in subverting host autophagy via dual mechanisms. SopB is a phosphoinositide phosphatase capable of altering the phosphoinositide dynamics of the host cell. Here, we demonstrate that SopB mediates escape from autophagy by inhibiting the terminal fusion of Salmonella-containing vacuoles (SCVs) with lysosomes and/or autophagosomes. We also report that SopB downregulates overall lysosomal biogenesis by modulating the Akt-transcription factor EB (TFEB) axis via restricting the latter's nuclear localisation. TFEB is a master regulator of lysosomal biogenesis and autophagy. This reduces the overall lysosome content inside host macrophages, further facilitating the survival of Salmonella in macrophages and systemic dissemination of Salmonella.
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