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The lack of effective malaria vaccines and recently increasing malaria cases urge innovative approaches to prevent malaria. Previously, we reported that the extract from the soil-dwelling fungus <jats:italic>Purpureocillium lilacinum<\/jats:italic>, a common fungus from the soil, reduced <jats:italic>Plasmodium falciparum<\/jats:italic> oocysts in <jats:italic>Anopheles gambiae<\/jats:italic> midguts after mosquitoes contacted the treated surface before feeding.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We used liquid chromatography to fraction fungal crude extract and tract the active fraction using a contact-wise approach and standard membrane feeding assays. The purified small molecules were analyzed using precise mass spectrometry and tandem mass spectrometry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We isolated four active small molecules from <jats:italic>P.\u00a0lilacinum<\/jats:italic> and determined them as leucinostatin A, B, A2, and B2. Pre-exposure of mosquitoes via contact with very low-concentration leucinostatin A significantly reduced the number of oocysts. The half-maximal response or inhibition concentration (EC<jats:sub>50<\/jats:sub>) via pre-exposure was 0.7 mg\/m<jats:sup>2<\/jats:sup>, similar to atovaquone but lower than other known antimalarials. The inhibitory effect of leucinostatin A against <jats:italic>P.\u00a0falciparum<\/jats:italic> during intraerythrocytic development, gametogenesis, sporogonic development, and ookinete formation, with the exception of oocyst development, suggests that leucinostatins play a part during parasite invasion of new cells.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Leucinostatins, secondary metabolites from <jats:italic>P.\u00a0lilacinum<\/jats:italic> disrupt malaria development, particular transmission to mosquitoes by contact. The contact-wise malaria control as a nonconventional approach is highly needed in malaria-endemic areas.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s13071-024-06450-y","type":"journal-article","created":{"date-parts":[[2024,9,20]],"date-time":"2024-09-20T09:02:02Z","timestamp":1726822922000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Leucinostatins from fungal extracts block malaria transmission to mosquitoes"],"prefix":"10.1186","volume":"17","author":[{"given":"Guodong","family":"Niu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenda","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,20]]},"reference":[{"key":"6450_CR1","unstructured":"Programme GM: World malaria report 2022. 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