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Differential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasion.
- Source :
-
Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases [Infect Genet Evol] 2014 Dec; Vol. 28, pp. 635-47. Date of Electronic Publication: 2014 Jun 11. - Publication Year :
- 2014
-
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.<br /> (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Anopheles genetics
Evolution, Molecular
Gastrointestinal Tract metabolism
Gene Expression
Genetic Variation
Insect Proteins chemistry
Insect Proteins genetics
Molecular Sequence Data
Selection, Genetic
Sequence Alignment
Anopheles metabolism
Anopheles parasitology
Insect Proteins metabolism
Malaria, Falciparum transmission
Malaria, Vivax transmission
Plasmodium falciparum pathogenicity
Plasmodium vivax pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 1567-7257
- Volume :
- 28
- Database :
- MEDLINE
- Journal :
- Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 24929123
- Full Text :
- https://doi.org/10.1016/j.meegid.2014.05.025