{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T01:11:32Z","timestamp":1784682692206,"version":"3.55.0"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_212795 and CRII5_198543\/2"],"award-info":[{"award-number":["310030_212795 and CRII5_198543\/2"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018987","name":"MCID","doi-asserted-by":"crossref","award":["MA-09"],"award-info":[{"award-number":["MA-09"]}],"id":[{"id":"10.13039\/100018987","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Malaria, caused by Plasmodium parasites, remains a global health crisis, necessitating novel therapeutic strategies targeting host\u2013parasite interactions. During liver-stage infection, parasites exploit host vesicular trafficking machinery, particularly SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins that mediate membrane fusion. Using a CRISPR\/Cas9 knockout system in HeLa cells combined with advanced microscopy of Plasmodium berghei-infected HeLa cells, we identified specific endolysosomal SNAREs including Vesicle-Associated Membrane Protein 7 (VAMP7), Vesicle-Associated Membrane Protein 8 (VAMP8), Vesicle Transport Through Interaction With T-SNAREs 1B (Vti1B), and Syntaxin 7 (Stx7) to be recruited to the parasitophorous vacuole membrane (PVM) with distinct temporal profiles. This demonstrates the parasite\u2019s precise manipulation of host endolysosomal trafficking pathways. VAMP7 and Vti1B were localized to the PVM within 30 min post-infection, suggesting potential roles during invasion, while VAMP8 and Stx7 appeared later around 24 h post infection (hpi), coinciding with increased nutrient acquisition. Single gene deletions showed minimal impact, but combinatorial knockouts (KO) revealed critical redundancy. VAMP7-VAMP8 as well as VAMP7\u2013Vti1B double KO significantly reduced parasite infection and growth, with Vti1B playing a dominant role. Triple KO phenotypes mirrored VAMP7-Vti1B disruption, underscoring Vti1B\u2019s dominant role. SNARE depletion also impaired the lysosome\u2013PVM association and LAMP1 positive vesicle recruitment. Our findings indicate Plasmodium hijacks a coordinated host SNARE network to fuse lysosomes with the PVM for nutrient uptake. Targeting Vti1B-containing complexes disrupts this pathway without host cell toxicity, offering a promising host-directed antimalarial approach.<\/jats:p>","DOI":"10.3390\/cells15070584","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:05:33Z","timestamp":1774451133000},"page":"584","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Host SNARE Proteins Mediate Lysosome and PVM Fusion to Support Plasmodium Liver Infection"],"prefix":"10.3390","volume":"15","author":[{"given":"Kodzo","family":"Atchou","sequence":"first","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-0040","authenticated-orcid":false,"given":"Nicolas","family":"Kramer","sequence":"additional","affiliation":[{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annina","family":"Bindschedler","sequence":"additional","affiliation":[{"name":"Graduate School for Cellular and Biomedical Sciences, University of Bern, Mittelstrasse 43, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8721-1163","authenticated-orcid":false,"given":"Jacqueline","family":"Schmuckli-Maurer","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Caldelari","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker T.","family":"Heussler","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e214","DOI":"10.1016\/S2666-5247(24)00016-8","article-title":"The 2023 WHO World malaria report","volume":"5","author":"Venkatesan","year":"2024","journal-title":"Lancet Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1371\/journal.ppat.0030171","article-title":"Release of hepatic Plasmodium yoelii merozoites into the pulmonary microvasculature","volume":"3","author":"Baer","year":"2007","journal-title":"PLoS Pathog."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1038\/nrmicro1529","article-title":"The silent path to thousands of merozoites: The Plasmodium liver stage","volume":"4","author":"Rodriguez","year":"2006","journal-title":"Nat. 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