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.
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Infection, Genetics and Evolution
