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Mosquito, and other insects, utilize salivary proteins to regulate these responses at the bite site during and after blood feeding. We investigated the function of <jats:italic>Anopheles gambiae<\/jats:italic> salivary apyrase (AgApyrase) in regulating hemostasis in the mosquito blood meal and in <jats:italic>Plasmodium<\/jats:italic> transmission. Our results demonstrate that salivary apyrase, a known inhibitor of platelet aggregation, interacts with and activates tissue plasminogen activator, facilitating the conversion of plasminogen to plasmin, a human protease that degrades fibrin and facilitates <jats:italic>Plasmodium<\/jats:italic> transmission. We show that mosquitoes ingest a substantial amount of apyrase during blood feeding, which reduces coagulation in the blood meal by enhancing fibrin degradation and inhibiting platelet aggregation. AgApyrase significantly enhanced <jats:italic>Plasmodium<\/jats:italic> infection in the mosquito midgut, whereas AgApyrase immunization inhibited <jats:italic>Plasmodium<\/jats:italic> mosquito infection and sporozoite transmission. This study highlights a pivotal role for mosquito salivary apyrase for regulation of hemostasis in the mosquito blood meal and for <jats:italic>Plasmodium<\/jats:italic> transmission to mosquitoes and to the mammalian host, underscoring the potential for strategies to prevent malaria transmission.<\/jats:p>","DOI":"10.1038\/s41467-024-52502-3","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T22:55:51Z","timestamp":1726786551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mosquito salivary apyrase regulates blood meal hemostasis and facilitates malaria parasite transmission"],"prefix":"10.1038","volume":"15","author":[{"given":"Zarna Rajeshkumar","family":"Pala","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Luiz","family":"Alves e Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahnaz","family":"Minai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Crews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Patino-Martinez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7706-1464","authenticated-orcid":false,"given":"Carmelo","family":"Carmona-Rivera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5740-5178","authenticated-orcid":false,"given":"Paola Carolina","family":"Valenzuela Leon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Martin-Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yevel","family":"Flores-Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9260-2102","authenticated-orcid":false,"given":"Raul E.","family":"Cachau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Muslinkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apostolos G.","family":"Gittis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naman","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"Garboczi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derron A.","family":"Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-0815","authenticated-orcid":false,"given":"Mariana J.","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-2730","authenticated-orcid":false,"given":"Eric","family":"Calvo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9576-0058","authenticated-orcid":false,"given":"Joel","family":"Vega-Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,18]]},"reference":[{"key":"52502_CR1","unstructured":"WHO. 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