title: Plasmodium falciparum ookinetes require mosquito midgut chondroitin sulfate proteoglycans for cell invasion.
abstract: Malaria transmission entails development of the Plasmodium parasite in its insect vector, the Anopheles mosquito. Parasite invasion of the mosquito midgut is the critical first step and involves adhesion to host epithelial cell ligands. Partial evidence suggests that midgut oligosaccharides are important ligands for parasite adhesion; however, the identity of these glycans remains unknown. We have identified a population of chondroitin glycosaminoglycans along the apical midgut microvilli of Anopheles gambiae and further demonstrated ookinete recognition of these glycans in vitro. By repressing the expression of the peptide-O-xylosyltransferase homolog of An. gambiae by means of RNA interference, we blocked glycosaminoglycan chain biosynthesis, diminished chondroitin sulfate levels in the adult midgut, and substantially inhibited parasite development. We provide evidence for the in vivo role of chondroitin sulfate proteoglycans in Plasmodium falciparum invasion of the midgut and insight into the molecular mechanisms mediating parasite-mosquito interactions.
authors.affiliation: Department of Molecular Microbiology and Immunology, Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA. rdinglas@jhsph.edu
authors.forename: Rhoel R
authors.initials: RR
authors.lastname: Dinglasan
authors.forename: Aditi
authors.initials: A
authors.lastname: Alaganan
authors.forename: Anil K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Akio
authors.initials: A
authors.lastname: Saito
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D000818:Animals; D000852:Anopheles / Q000382:microbiology*; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology; D004064:Digestive System / Q000166:cytology / Q000382:microbiology*; D006025:Glycosaminoglycans / Q000502:physiology; D006801:Humans; D016778:Malaria, Falciparum / Q000635:transmission*; D008871:Microvilli / Q000382:microbiology / Q000502:physiology / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D034622:RNA Interference
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D006025:Glycosaminoglycans