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EMBO J. 2013 Nov 27;32(23):3066-78. doi: 10.1038/emboj.2013.234. Epub 2013 Oct 25.

Listeria phospholipases subvert host autophagic defenses by stalling pre-autophagosomal structures.

Author information

1
1] Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada [2] Department of Immunology, University of Toronto, Toronto, Canada.

Abstract

Listeria can escape host autophagy defense pathways through mechanisms that remain poorly understood. We show here that in epithelial cells, Listeriolysin (LLO)-dependent cytosolic escape of Listeria triggered a transient amino-acid starvation host response characterized by GCN2 phosphorylation, ATF3 induction and mTOR inhibition, the latter favouring a pro-autophagic cellular environment. Surprisingly, rapid recovery of mTOR signalling was neither sufficient nor necessary for Listeria avoidance of autophagic targeting. Instead, we observed that Listeria phospholipases PlcA and PlcB reduced autophagic flux and phosphatidylinositol 3-phosphate (PI3P) levels, causing pre-autophagosomal structure stalling and preventing efficient targeting of cytosolic bacteria. In co-infection experiments, wild-type Listeria protected PlcA/B-deficient bacteria from autophagy-mediated clearance. Thus, our results uncover a critical role for Listeria phospholipases C in the inhibition of autophagic flux, favouring bacterial escape from host autophagic defense.

PMID:
24162724
PMCID:
PMC3844955
DOI:
10.1038/emboj.2013.234
[Indexed for MEDLINE]
Free PMC Article

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