An epigenetic antimalarial resistance mechanism involving parasite genes linked to nutrient uptake.

ABSTRACT: Acquired antimalarial drug resistance produces treatment failures and has led to periods of global disease resurgence. In Plasmodium falciparum, resistance is known to arise through genome-level changes such as mutations and gene duplications. We now report an epigenetic resistance mechanism involving genes responsible for the plasmodial surface anion channel, a nutrient channel that also transports ions and antimalarial compounds at the host erythrocyte membrane. Two blasticidin S-resistant lines exhibited markedly reduced expression of clag genes linked to channel activity, but had no genome-level changes. Silencing aborted production of the channel protein and was directly responsible for reduced uptake. Silencing affected clag paralogs on two chromosomes and was mediated by specific hi

SUBMITTER: Sharma P 

PROVIDER: S-EPMC3707646 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature