title: A combined transcriptome and proteome survey of malaria parasite liver stages.
abstract: For 50 years since their discovery, the malaria parasite liver stages (LS) have been difficult to analyze, impeding their utilization as a critical target for antiinfection vaccines and drugs. We have undertaken a comprehensive transcriptome analysis in combination with a proteomic survey of LS. Green fluorescent protein-tagged Plasmodium yoelii (PyGFP) was used to efficiently isolate LS-infected hepatocytes from the rodent host. Genome-wide LS gene expression was profiled and compared with other parasite life cycle stages. The analysis revealed approximately 2,000 genes active during LS development, and proteomic analysis identified 816 proteins. A subset of proteins appeared to be expressed in LS only. The data revealed exported parasite proteins and LS metabolic pathways including expression of FASII pathway enzymes. The FASII inhibitor hexachlorophene and the antibiotics, tetracycline and rifampicin, that target the apicoplast inhibited LS development, identifying FASII and other pathways localized in the apicoplast as potential drug targets to prevent malaria infection.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Tarun
authors.forename: Xinxia
authors.initials: X
authors.lastname: Peng
authors.forename: Ronald F
authors.initials: RF
authors.lastname: Dumpit
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ogata
authors.forename: Hilda
authors.initials: H
authors.lastname: Silva-Rivera
authors.forename: Nelly
authors.initials: N
authors.lastname: Camargo
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Daly
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Bergman
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000818:Animals; D015195:Drug Design; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000737:chemistry; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D008099:Liver / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology*; D016366:Open Reading Frames; D010967:Plasmodium yoelii / Q000378:metabolism; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D014158:Transcription, Genetic
chemical_list: D005227:Fatty Acids; D020543:Proteome; D049452:Green Fluorescent Proteins