{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T01:41:07Z","timestamp":1783561267074,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011783","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000}}],"reference-count":86,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI127465 (ZQL)"],"award-info":[{"award-number":["R01AI127465 (ZQL)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Legionella pneumophila<\/jats:italic> strains harboring wild-type <jats:italic>rpsL<\/jats:italic> such as Lp02<jats:italic>rpsL<\/jats:italic><jats:sub>WT<\/jats:sub> cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR\/Cas9 screening, we identified <jats:italic>Hmg20a<\/jats:italic> and <jats:italic>Nol9<\/jats:italic> as host factors important for restricting strain Lp02<jats:italic>rpsL<\/jats:italic><jats:sub>WT<\/jats:sub> in BMDMs. Depletion of <jats:italic>Hmg20a<\/jats:italic> protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by <jats:italic>Hmg20a<\/jats:italic> was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot\/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02<jats:italic>rpsL<\/jats:italic><jats:sub>WT<\/jats:sub> in BMDMs. Our results establish that <jats:italic>L<\/jats:italic>. <jats:italic>pneumophila<\/jats:italic> exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011783","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T17:38:10Z","timestamp":1715621890000},"page":"e1011783","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7"],"prefix":"10.1371","volume":"20","author":[{"given":"Chuang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8890-6621","authenticated-orcid":true,"given":"Zhao-Qing","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"issue":"3","key":"ppat.1011783.ref001","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/nri.2016.147","article-title":"Programmed cell death as a defence against infection","volume":"17","author":"I Jorgensen","year":"2017","journal-title":"Nat Rev 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