title: Total and putative surface proteomics of malaria parasite salivary gland sporozoites.
abstract: Malaria infections of mammals are initiated by the transmission of Plasmodium salivary gland sporozoites during an Anopheles mosquito vector bite. Sporozoites make their way through the skin and eventually to the liver, where they infect hepatocytes. Blocking this initial stage of infection is a promising malaria vaccine strategy. Therefore, comprehensively elucidating the protein composition of sporozoites will be invaluable in identifying novel targets for blocking infection. Previous efforts to identify the proteins expressed in Plasmodium mosquito stages were hampered by the technical difficulty of separating the parasite from its vector; without effective purifications, the large majority of proteins identified were of vector origin. Here we describe the proteomic profiling of highly purified salivary gland sporozoites from two Plasmodium species: human-infective Plasmodium falciparum and rodent-infective Plasmodium yoelii. The combination of improved sample purification and high mass accuracy mass spectrometry has facilitated the most complete proteome coverage to date for a pre-erythrocytic stage of the parasite. A total of 1991 P. falciparum sporozoite proteins and 1876 P. yoelii sporozoite proteins were identified, with >86% identified with high sequence coverage. The proteomic data were used to confirm the presence of components of three features critical for sporozoite infection of the mammalian host: the sporozoite motility and invasion apparatus (glideosome), sporozoite signaling pathways, and the contents of the apical secretory organelles. Furthermore, chemical labeling and identification of proteins on live sporozoites revealed previously uncharacterized complexity of the putative sporozoite surface-exposed proteome. Taken together, the data constitute the most comprehensive analysis to date of the protein expression of salivary gland sporozoites and reveal novel potential surface-exposed proteins that might be valuable targets for antibody blockage of infection.
authors: Malaria Program, Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, Washington 98109, USA.
authors: Scott E
authors: SE
authors: Lindner
authors: Kristian E
authors: KE
authors: Swearingen
authors: Anke
authors: A
authors: Harupa
authors: Ashley M
authors: AM
authors: Vaughan
authors: Photini
authors: P
authors: Sinnis
authors: Robert L
authors: RL
authors: Moritz
authors: Stefan H I
authors: SH
authors: Kappe
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D020013:Calcium Signaling; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D006790:Host-Parasite Interactions; D007303:Insect Vectors / Q000469:parasitology*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D010963:Plasmodium falciparum / Q000378:metabolism; D010967:Plasmodium yoelii / Q000378:metabolism; D020543:Proteome / Q000302:isolation & purification / Q000378:metabolism*; D040901:Proteomics; D015800:Protozoan Proteins / Q000302:isolation & purification / Q000378:metabolism*; D012469:Salivary Glands / Q000469:parasitology*; D055571:Secretory Pathway; D034101:Sporozoites / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D020543:Proteome; D015800:Protozoan Proteins