{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:33:36Z","timestamp":1790879616930,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012636","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000}}],"reference-count":83,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-186114"],"award-info":[{"award-number":["PJT-186114"]}],"id":[{"id":"10.13039\/501100000024","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>Leishmania<\/jats:italic> is a vacuolar pathogen that replicates within parasitophorous vacuoles inside host phagocytes. To promote its replication, <jats:italic>Leishmania<\/jats:italic> relies on a panoply of strategies to acquire macromolecules such as lipids from host macrophages. In this study, we have evaluated the role of VAPA, an endoplasmic reticulum-resident membrane protein involved in inter-organellar lipid transport, in macrophages infected with <jats:italic>L. amazonensis<\/jats:italic>. Following infection of bone marrow-derived macrophages with <jats:italic>L. amazonensis<\/jats:italic> metacyclic promastigotes, we observed that VAPA gradually associates with communal parasitophorous vacuoles. Knockdown of VAPA prevented the replication of <jats:italic>L. amazonensis<\/jats:italic>, which was accompanied by an impaired parasitophorous vacuole expansion. Using fluorescent ceramide, we established that VAPA is required for the transport of sphingolipids to the parasitophorous vacuoles and for its acquisition by <jats:italic>L. amazonensis<\/jats:italic> amastigotes. Proximity-ligation assays revealed that <jats:italic>L. amazonensis<\/jats:italic> hijacks VAPA by disrupting its interactions with the host cell lipid transfer proteins CERT and ORP1L. Finally, we found that VAPA is essential for the transfer of the <jats:italic>Leishmania<\/jats:italic> virulence glycolipid lipophosphoglycan from the parasitophorous vacuoles to the host cell endoplasmic reticulum. We propose that VAPA contributes to the ability of <jats:italic>L. amazonensis<\/jats:italic> to colonize macrophages by mediating bi-directional transfer of lipids essential for parasite replication and virulence between the parasitophorous vacuoles and the host cell endoplasmic reticulum.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012636","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T20:52:39Z","timestamp":1743454359000},"page":"e1012636","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["VAPA mediates lipid exchange between Leishmania amazonensis and host macrophages"],"prefix":"10.1371","volume":"21","author":[{"given":"Ilona","family":"Gdovinova","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0633-5309","authenticated-orcid":true,"given":"Albert","family":"Descoteaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"issue":"9185","key":"ppat.1012636.ref001","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S0140-6736(98)10178-2","article-title":"Leishmaniasis","volume":"354","author":"BL Herwaldt","year":"1999","journal-title":"Lancet"},{"issue":"12","key":"ppat.1012636.ref002","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1084\/jem.185.12.2061","article-title":"Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan","volume":"185","author":"M 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