Differential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasion

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. 
Publication PDF: 
Derrick K. Mathias, Juliette G. Jardim, Lindsay A. Parish , Jennifer S. Armistead , Hung V. Trinh, Chalermpon Khumpitak, Jetsumon Sattabongkot, Rhoel R. Dinglasan
Infection, Genetics and Evolution




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