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dc.contributor.authorOkuda, Kendi
dc.contributor.authorSilva Costa Franco, Miriam Maria
dc.contributor.authorYasunaga, Ari
dc.contributor.authorGazzinelli, Ricardo T
dc.contributor.authorRabinovitch, Michel
dc.contributor.authorCherry, Sara
dc.contributor.authorSilverman, Neal
dc.date.accessioned2024-01-10T16:34:09Z
dc.date.available2024-01-10T16:34:09Z
dc.date.issued2022-08-13
dc.identifier.citationOkuda K, Silva Costa Franco MM, Yasunaga A, Gazzinelli R, Rabinovitch M, Cherry S, Silverman N. Leishmania amazonensis sabotages host cell SUMOylation for intracellular survival. iScience. 2022 Aug 13;25(9):104909. doi: 10.1016/j.isci.2022.104909. PMID: 36060064; PMCID: PMC9436752.en_US
dc.identifier.eissn2589-0042
dc.identifier.doi10.1016/j.isci.2022.104909en_US
dc.identifier.pmid36060064
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52934
dc.description.abstractLeishmania parasites use elaborate virulence mechanisms to invade and thrive in macrophages. These virulence mechanisms inhibit host cell defense responses and generate a specialized replicative niche, the parasitophorous vacuole. In this work, we performed a genome-wide RNAi screen in Drosophila macrophage-like cells to identify the host factors necessary for Leishmania amazonensis infection. This screen identified 52 conserved genes required specifically for parasite entry, including several components of the SUMOylation machinery. Further studies in mammalian macrophages found that L. amazonensis infection inhibited SUMOylation within infected macrophages and this inhibition enhanced parasitophorous vacuole growth and parasite proliferation through modulation of multiple genes especially ATP6V0D2, which in turn affects CD36 expression and cholesterol levels. Together, these data suggest that parasites actively sabotage host SUMOylation and alter host transcription to improve their intracellular niche and enhance their replication.en_US
dc.language.isoenen_US
dc.relation.ispartofiScienceen_US
dc.relation.urlhttps://doi.org/10.1016/j.isci.2022.104909en_US
dc.rightsCopyright 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectImmunologyen_US
dc.subjectParasitologyen_US
dc.titleLeishmania amazonensis sabotages host cell SUMOylation for intracellular survivalen_US
dc.typeJournal Articleen_US
dc.source.journaltitleiScience
dc.source.volume25
dc.source.issue9
dc.source.beginpage104909
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journaliScience
refterms.dateFOA2024-01-10T16:35:03Z
dc.contributor.departmentMedicineen_US


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Copyright 2022 The Authors.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).