{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Okuda K"],"funding":["National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","National Institutes of Health"],"pagination":["104909"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9436752"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(9)"],"pubmed_abstract":["<i>Leishmania</i> 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 <i>Drosophila</i> macrophage-like cells to identify the host factors necessary for <i>Leishmania amazonensis</i> 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 <i>L. amazonensis</i> infection inhibited SUMOylation within infected macrophages and this inhibition enhanced parasitophorous vacuole growth and parasite proliferation through modulation of multiple genes especially <i>ATP6V0D2</i>, which in turn affects <i>CD36</i> 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."],"journal":["iScience"],"pubmed_title":["<i>Leishmania amazonensis</i> sabotages host cell SUMOylation for intracellular survival."],"pmcid":["PMC9436752"],"funding_grant_id":["R21 AI136532","R21AI136532","R21 AI154208","R21AI154208","R21 AI109678","R56 AI165847"],"pubmed_authors":["Cherry S","Silverman N","Okuda K","Gazzinelli R","Rabinovitch M","Yasunaga A","Silva Costa Franco MM"],"additional_accession":[]},"is_claimable":false,"name":"<i>Leishmania amazonensis</i> sabotages host cell SUMOylation for intracellular survival.","description":"<i>Leishmania</i> 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 <i>Drosophila</i> macrophage-like cells to identify the host factors necessary for <i>Leishmania amazonensis</i> 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 <i>L. amazonensis</i> infection inhibited SUMOylation within infected macrophages and this inhibition enhanced parasitophorous vacuole growth and parasite proliferation through modulation of multiple genes especially <i>ATP6V0D2</i>, which in turn affects <i>CD36</i> 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Sep","modification":"2026-05-28T03:28:12.355Z","creation":"2025-02-19T00:44:08.191Z"},"accession":"S-EPMC9436752","cross_references":{"pubmed":["36060064"],"doi":["10.1016/j.isci.2022.104909"]}}