Chemical Genomics Profiling of Antimalarial Drugs

Chemical Genomics Profiling is based on the premise that diploid yeast containing a gene expressed in heterozygosis will become hypersensitive to sub-lethal doses of an inhibitor targeting the product of this gene. Violacein is a natural compound known for its biological activity against cancer cells and several pathogens, including the malaria parasite, Plasmodium falciparum (Pf). Here, we used CGP to narrow down the mechanism of action of violacein. We cultured pools of ~ 6,000 barcoded heterozygous yeast strains in the presence of violacein or DMSO (vehicle control) for 5 and 10 generations , extracted and amplified the genomic DNA and performed deep barcode sequencing.