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

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

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