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Infect Genet Evol. 2014 Dec;28:635-47. doi: 10.1016/j.meegid.2014.05.025. Epub 2014 Jun 11.

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

Author information

1
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health & Malaria Research Institute, Baltimore, MD 21205, USA. Electronic address: dmathia2@jhu.edu.
2
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health & Malaria Research Institute, Baltimore, MD 21205, USA. Electronic address: juliettejardim@gmail.com.
3
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health & Malaria Research Institute, Baltimore, MD 21205, USA. Electronic address: lindsayannparish@gmail.com.
4
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health & Malaria Research Institute, Baltimore, MD 21205, USA. Electronic address: armistead.j@wehi.edu.au.
5
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health & Malaria Research Institute, Baltimore, MD 21205, USA. Electronic address: hungvtrinh@gmail.com.
6
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: chalermpon.kum@mahidol.ac.th.
7
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: jetsumon@hotmail.com.
8
W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health & Malaria Research Institute, Baltimore, MD 21205, USA. Electronic address: rdinglas@jhsph.edu.

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.

KEYWORDS:

Anopheles; Malaria; Midgut; Plasmodium falciparum; Plasmodium vivax; Transmission-blocking

PMID:
24929123
PMCID:
PMC4257886
DOI:
10.1016/j.meegid.2014.05.025
[Indexed for MEDLINE]
Free PMC Article

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