A combined transcriptome and proteome survey of malaria parasite liver stages
Autor: | Ronald F. Dumpit, Nelly Camargo, Xinxia Peng, Thomas M. Daly, Yuko Ogata, Lawrence W. Bergman, Alice S. Tarun, Stefan H. I. Kappe, Hilda Silva-Rivera |
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Rok vydání: | 2008 |
Předmět: |
Proteomics
Proteome Transcription Genetic Green Fluorescent Proteins Biology Microbiology Transcriptome Open Reading Frames Gene expression Animals Humans Parasite hosting Gene Apicoplast Multidisciplinary Fatty Acids Plasmodium yoelii Biological Sciences biology.organism_classification Molecular biology Malaria Gene Expression Regulation Liver Drug Design Hepatocytes |
Zdroj: | Proceedings of the National Academy of Sciences. 105:305-310 |
ISSN: | 1091-6490 0027-8424 |
DOI: | 10.1073/pnas.0710780104 |
Popis: | 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 ≈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. |
Databáze: | OpenAIRE |
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