Abstract：
: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 IC(50) 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.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Yuan J,Johnson RL,Huang R,Wichterman J,Jiang H,Hayton K,Fidock DA,Wellems TE,Inglese J,Austin CP,Su XZdoi
10.1038/nchembio.215subject
Has Abstractpub_date
2009-10-01 00:00:00pages
765-71issue
10eissn
1552-4450issn
1552-4469pii
nchembio.215journal_volume
5pub_type
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