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dc.contributor.authorDerrick K. Mathiasen_US
dc.contributor.authorJuliette G. Jardimen_US
dc.contributor.authorLindsay A. Parishen_US
dc.contributor.authorJennifer S. Armisteaden_US
dc.contributor.authorHung V. Trinhen_US
dc.contributor.authorChalermpon Kumpitaken_US
dc.contributor.authorJetsumon Sattabongkoten_US
dc.contributor.authorRhoel R. Dinglasanen_US
dc.contributor.otherJohns Hopkins Bloomberg School of Public Healthen_US
dc.contributor.otherMahidol Universityen_US
dc.identifier.citationInfection, Genetics and Evolution. Vol.28, (2014), 635-647en_US
dc.description.abstract© 2014 Elsevier B.V. Novel strategies to directly thwart malaria transmission are needed to maintain the gains achieved by current control measures. Transmission-blocking interventions (TBIs), namely vaccines and drugs targeting parasite or mosquito molecules required for vector-stage parasite development, have been recognized as promising approaches for preventing malaria transmission. However, the number of TBI targets is limited and their degree of conservation among the major vector-parasite systems causing human disease is unclear. Therefore, discovery and characterization of novel proteins involved in vector-stage parasite development of Plasmodium falciparum and Plasmodium vivax is paramount. We mined the recent Anopheles gambiae midgut lipid raft proteome for putative mosquito-derived TBI targets and characterized a secreted glycoconjugate of unknown function, AgSGU. We analyzed molecular variation in this protein among a range of anopheline mosquitoes, determined its transcriptomic and proteomic profiles, and conducted both standard and direct membrane feeding assays with P. falciparum (lab/field) and P. vivax (field) in An. gambiae and Anopheles dirus. We observed that α-AgSGU antibodies significantly reduced midgut infection intensity for both lab and field isolates of P. falciparum in An. gambiae and An. dirus. However, no transmission-reducing effects were noted when comparable concentrations of antibodies were included in P. vivax-infected blood meals. Although antibodies against AgSGU exhibit transmission-reducing activity, the high antibody titer required for achieving 80% reduction in oocyst intensity precludes its consideration as a malaria mosquito-based TBI candidate. However, our results suggest that P. falciparum and P. vivax ookinetes use a different repertoire of midgut surface glycoproteins for invasion and that α-AgSGU antibodies, as well as antibodies to other mosquito-midgut microvillar surface proteins, may prove useful as tools for interrogating Plasmodium-mosquito interactions.en_US
dc.rightsMahidol Universityen_US
dc.subjectAgricultural and Biological Sciencesen_US
dc.subjectBiochemistry, Genetics and Molecular Biologyen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleDifferential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasionen_US
Appears in Collections:Scopus 2011-2015

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