title: 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.
authors.affiliation: 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.
authors.forename: Derrick K
authors.initials: DK
authors.lastname: Mathias
authors.affiliation: 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.
authors.forename: Juliette G
authors.initials: JG
authors.lastname: Jardim
authors.affiliation: 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.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Parish
authors.affiliation: 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.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Armistead
authors.affiliation: 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.
authors.forename: Hung V
authors.initials: HV
authors.lastname: Trinh
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: chalermpon.kum@mahidol.ac.th.
authors.forename: Chalermpon
authors.initials: C
authors.lastname: Kumpitak
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: jetsumon@hotmail.com.
authors.forename: Jetsumon
authors.initials: J
authors.lastname: Sattabongkot
authors.affiliation: 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.
authors.forename: Rhoel R
authors.initials: RR
authors.lastname: Dinglasan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology*; D019143:Evolution, Molecular; D041981:Gastrointestinal Tract / Q000378:metabolism; D015870:Gene Expression; D014644:Genetic Variation; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000635:transmission*; D016780:Malaria, Vivax / Q000635:transmission*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000472:pathogenicity*; D010966:Plasmodium vivax / Q000472:pathogenicity*; D012641:Selection, Genetic; D016415:Sequence Alignment
chemical_list: D019476:Insect Proteins
keywords: Anopheles; Malaria; Midgut; Plasmodium falciparum; Plasmodium vivax; Transmission-blocking