{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T08:11:18Z","timestamp":1780647078157,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010324","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,2,17]],"date-time":"2022-02-17T00:00:00Z","timestamp":1645056000000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T00:00:00Z","timestamp":1644192000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI073904"],"award-info":[{"award-number":["R01AI073904"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>The bacterial pathogen <jats:italic>Shigella flexneri<\/jats:italic> causes 270 million cases of bacillary dysentery worldwide every year, resulting in more than 200,000 deaths. <jats:italic>S<\/jats:italic>. <jats:italic>flexneri<\/jats:italic> pathogenic properties rely on its ability to invade epithelial cells and spread from cell to cell within the colonic epithelium. This dissemination process relies on actin-based motility in the cytosol of infected cells and formation of membrane protrusions that project into adjacent cells and resolve into double-membrane vacuoles (DMVs) from which the pathogen escapes, thereby achieving cell-to-cell spread. <jats:italic>S<\/jats:italic>. <jats:italic>flexneri<\/jats:italic> dissemination is facilitated by the type 3 secretion system (T3SS) through poorly understood mechanisms. Here, we show that the T3SS effector IpgD facilitates the resolution of membrane protrusions into DMVs during <jats:italic>S<\/jats:italic>. <jats:italic>flexneri<\/jats:italic> dissemination. The phosphatidylinositol 4-phosphatase activity of IpgD decreases PtdIns(4,5)P<jats:sub>2<\/jats:sub> levels in membrane protrusions, thereby counteracting <jats:italic>de novo<\/jats:italic> cortical actin formation in protrusions, a process that restricts the resolution of protrusions into DMVs. Finally, using an infant rabbit model of shigellosis, we show that IpgD is required for efficient cell-to-cell spread <jats:italic>in vivo<\/jats:italic> and contributes to the severity of dysentery.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010324","type":"journal-article","created":{"date-parts":[[2022,2,7]],"date-time":"2022-02-07T18:37:47Z","timestamp":1644259067000},"page":"e1010324","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["The type 3 secretion effector IpgD promotes S. flexneri dissemination"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-5855","authenticated-orcid":true,"given":"Volkan K.","family":"K\u00f6seo\u011flu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5045-6725","authenticated-orcid":true,"given":"Marieke K.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-0218","authenticated-orcid":true,"given":"Herv\u00e9","family":"Agaisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,7]]},"reference":[{"issue":"23","key":"ppat.1010324.ref001","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1056\/NEJMra041837","article-title":"Contagious acute gastrointestinal infections","volume":"351","author":"DM Musher","year":"2004","journal-title":"N Engl J Med"},{"issue":"10122","key":"ppat.1010324.ref002","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/S0140-6736(17)33296-8","volume":"391","author":"KL Kotloff","year":"2018","journal-title":"Shigellosis. 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