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Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum

热1 shanleicn 添加于 2009-11-27 07:49 | 1856 次阅读 | 0 个评论

作者
Yuan J, Johnson RL, Huang R, Wichterman J, Jiang H, Hayton K, Fidock DA, Wellems TE, Inglese J, Austin CP, Su X-zhuan
摘要
Studies of gene function and molecular mechanisms in Plasmodium falciparum are hampered by difficulties in characterizing and measuring phenotypic differences between individual parasites. We screened seven parasite lines for differences in responses to 1,279 bioactive chemicals. Hundreds of compounds were active in inhibiting parasite growth; 607 differential chemical phenotypes, defined as pairwise IC50 differences of fivefold or more between parasite lines, were cataloged. We mapped major determinants for three differential chemical phenotypes between the parents of a genetic cross, and we identified target genes by fine mapping and testing the responses of parasites in which candidate genes were genetically replaced with mutant alleles. Differential sensitivity to dihydroergotamine methanesulfonate (1), a serotonin receptor antagonist, was mapped to a gene encoding the homolog of human P-glycoprotein (PfPgh-1). This study identifies new leads for antimalarial drugs and demonstrates the utility of a high-throughput chemical genomic strategy for studying malaria traits.
详细资料
- 文献种类:期刊
- 期刊名称: Nature Chemical Biology
- 期刊缩写: Nat Chem Biol
- 期卷页: 2009年第5卷第10期 765-771页
- ISBN: 1552-4450
标签

恶性疟原虫靶点
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附件
Genetic mapping of targets mediating differential chemical phenotypes in Plasmodium falciparum