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EMBO J. 2018 Dec 3;37(23). pii: e98529. doi: 10.15252/embj.201798529. Epub 2018 Nov 2.

Stress-induced host membrane remodeling protects from infection by non-motile bacterial pathogens.

Author information

1
Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany.
2
RNA Biology Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany.
3
Molecular Microbial Pathogenesis Laboratory, Institut Pasteur, Paris, France.
4
Functional Genomics and RNA-based Therapeutics, UC-BIOTECH, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
5
RNA & Infection Group, UC-BIOTECH, Center for Neuroscience and Cell Biology (CNC), University of Coimbra, Coimbra, Portugal.
6
Helmholtz Institute for RNA-Based Infection Research (HIRI), Würzburg, Germany.
7
Host RNA Metabolism Group, Institute for Molecular Infection Biology (IMIB), University of Würzburg, Würzburg, Germany ana.eulalio@uni-wuerzburg.de aeulalio@ci.uc.pt.

Abstract

While mucosal inflammation is a major source of stress during enteropathogen infection, it remains to be fully elucidated how the host benefits from this environment to clear the pathogen. Here, we show that host stress induced by different stimuli mimicking inflammatory conditions strongly reduces the binding of Shigella flexneri to epithelial cells. Mechanistically, stress activates acid sphingomyelinase leading to host membrane remodeling. Consequently, knockdown or pharmacological inhibition of the acid sphingomyelinase blunts the stress-dependent inhibition of Shigella binding to host cells. Interestingly, stress caused by intracellular Shigella replication also results in remodeling of the host cell membrane, in vitro and in vivo, which precludes re-infection by this and other non-motile pathogens. In contrast, Salmonella Typhimurium overcomes the shortage of permissive entry sites by gathering effectively at the remaining platforms through its flagellar motility. Overall, our findings reveal host membrane remodeling as a novel stress-responsive cell-autonomous defense mechanism that protects epithelial cells from infection by non-motile bacterial pathogens.

KEYWORDS:

Salmonella ; Shigella ; acid sphingomyelinase; host stress response; membrane remodeling

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