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Here, we show that host stress induced by different stimuli mimicking inflammatory conditions strongly reduces the binding of\n                    <jats:italic>Shigella flexneri<\/jats:italic>\n                    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\u2010dependent inhibition of\n                    <jats:italic>Shigella<\/jats:italic>\n                    binding to host cells. Interestingly, stress caused by intracellular\n                    <jats:italic>Shigella<\/jats:italic>\n                    replication also results in remodeling of the host cell membrane,\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    and\n                    <jats:italic>in\u00a0vivo<\/jats:italic>\n                    , which precludes re\u2010infection by this and other non\u2010motile pathogens. In contrast,\n                    <jats:italic>Salmonella<\/jats:italic>\n                    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\u2010responsive cell\u2010autonomous defense mechanism that protects epithelial cells from infection by non\u2010motile bacterial pathogens.\n                  <\/jats:p>","DOI":"10.15252\/embj.201798529","type":"journal-article","created":{"date-parts":[[2018,11,2]],"date-time":"2018-11-02T07:25:22Z","timestamp":1541143522000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Stress\u2010induced host membrane remodeling protects from infection by non\u2010motile bacterial pathogens"],"prefix":"10.1038","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1781-5591","authenticated-orcid":false,"given":"Caroline","family":"Tawk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Nigro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Rodrigues Lopes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clivia","family":"Lisowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1922-4824","authenticated-orcid":false,"given":"Miguel","family":"Mano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7542-4527","authenticated-orcid":false,"given":"Philippe","family":"Sansonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-1404","authenticated-orcid":false,"given":"J\u00f6rg","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7355-0674","authenticated-orcid":false,"given":"Ana","family":"Eulalio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,11,2]]},"reference":[{"key":"BFEMBJ201798529_CR1","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/path.1700250411","volume":"25","author":"FW Andrewes","year":"1922","unstructured":"Andrewes FW (1922) Studies in group\u2010agglutination I. 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