{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:11:28Z","timestamp":1778152288479,"version":"3.51.4"},"posted":{"date-parts":[[2026,5,4]]},"group-title":"Microbiology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Malaria control remains constrained by an incomplete understanding of the molecular interactions that enable\n                  <jats:italic>Plasmodium falciparum<\/jats:italic>\n                  transmission within mosquito vectors. Although blood-stage parasite biology has been extensively studied, the mosquito-stage processes required for transmission are less well defined. Here, we characterize a previously unannotated\n                  <jats:italic>Anopheles gambiae<\/jats:italic>\n                  midgut factor, Midgut Ookinete Binding Protein 1 (AgMOBP1; AGAP008138), and define its role in parasite infection. AgMOBP1 is a membrane-associated protein localized predominantly to the apical surface of midgut epithelial cells, is induced by blood feeding, and appears restricted to anopheline mosquitoes. Functional infection assays showed that exogenous recombinant AgMOBP1 enhanced\n                  <jats:italic>Plasmodium<\/jats:italic>\n                  infectivity by increasing midgut oocyst burden, whereas anti-AgMOBP1 antibodies significantly reduced infection, establishing AgMOBP1 as a host factor that promotes transmission. Using biochemical interaction assays, we identified the parasite binding partner of AgMOBP1 as the\n                  <jats:italic>P. falciparum<\/jats:italic>\n                  syntaxin-5\u2013like protein PfSyn5. Disruption of this interaction with anti-PfSyn5 polyclonal antibodies produced exceptionally potent transmission-blocking activity, with complete inhibition at 1 \u00b5g\/mL and an estimated IC50 of \u223c3 ng\/mL (\u223c20 pM). This potency is approximately one million-fold lower than the total IgG concentration in normal human plasma. Together, these findings identify a critical mosquito\u2013parasite molecular interface required for malaria transmission and establish the AgMOBP1\u2013PfSyn5 axis as a promising target for transmission-blocking vaccines, monoclonal antibodies, and other intervention strategies.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance Statement<\/jats:title>\n                  <jats:p>\n                    Interrupting malaria transmission requires a deeper mechanistic understanding of how\n                    <jats:italic>Plasmodium<\/jats:italic>\n                    parasites interact with their mosquito vectors. Here, we define a previously uncharacterized mosquito midgut factor, AgMOBP1, and identify its parasite binding partner, the\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    membrane protein PfSyn5. We show that this molecular interaction is required for efficient parasite transmission to\n                    <jats:italic>Anopheles<\/jats:italic>\n                    mosquitoes. Remarkably, antibodies against PfSyn5 completely blocked transmission at low concentrations, revealing exceptional functional potency. These findings uncover a previously unknown mosquito\u2013parasite invasion pathway and establish the AgMOBP1\u2013PfSyn5 interface as a high-value target for transmission-blocking vaccines, monoclonal antibodies, and next-generation malaria control strategies.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.01.722187","type":"posted-content","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:45:22Z","timestamp":1777952722000},"source":"Crossref","is-referenced-by-count":0,"title":["Disruption of the AgMOBP1\u2013PfSyn5 interface abolishes malaria transmission"],"prefix":"10.64898","author":[{"given":"Julian","family":"Ramelow","sequence":"first","affiliation":[{"name":"Herbert Wertheim College of Medicine, Biomedical Sciences Graduate Program, Florida International University, Miami, FL 33199, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guodong","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida International University, Miami, FL 33199, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luka","family":"Kostallas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Undergraduate Program, Florida International University, Miami, FL 33199, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliana","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida International University, Miami, FL 33199, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida International University, Miami, FL 33199, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-3393","authenticated-orcid":false,"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Herbert Wertheim College of Medicine, Biomedical Sciences Graduate Program, Florida International University, Miami, FL 33199, United States"},{"name":"Department of Biological Sciences, Florida International University, Miami, FL 33199, United States"},{"name":"Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026050703250660000_2026.05.01.722187v1.1","unstructured":"WHO, World Health Organization: World Malaria Report. 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