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

• Caroline Tawk ^[1] ; Giulia Nigro ^[3] ; Ines Rodrigues Lopes ^[2] ; Carmen Aguilar ^[1] ; Clivia Lisowski ^[1] ; Miguel Mano ^[2] ; Philippe Sansonetti ^[3] ; Jörg Vogel ^[1] ; Ana Eulalio ^[1]
  1. [1] University of Würzburg

     University of Würzburg

     Kreisfreie Stadt Würzburg, Alemania

     
  2. [2] Universidade de Coimbra

     Universidade de Coimbra

     Coimbra (Sé Nova), Portugal

     
  3. [3] 3 Molecular Microbial Pathogenesis Laboratory Institut Pasteur Paris France

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 37, Nº. 23, 2018
• Idioma: inglés
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  • 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.