Early Genomic Amplifications in Blood-Stages of ARMD Plasmodium falciparum Acquiring De Novo Drug Resistance [Genome variation]

ABSTRACT: While many molecular changes associated with commonly used antimalarials are known, there remain important questions on how parasites arrive at the correct causal molecular solutions in a haploid genome. We selected for resistance to DSM1, a novel dihydroorotate dehydrogenase (DHODH) inhibitor with a non-biological triazolopyrimidine scaffold, in P. falciparum with the Accelerated Resistance to Multiple Drugs (ARMD) trait. While direct sequencing revealed no mutations in the target DHODH gene, comparative genomic hybridizations from four independently selected DSM1-resistant clones showed a large, single 34-95kb amplification in each clone. Each amplified region always included the DHODH locus. The length of this region and the resulting 2- to 3-fold DHODH copy number increase were ver

ORGANISM(S): Plasmodium falciparum Dd2

SUBMITTER: Pradipsinh Rathod 

PROVIDER: E-GEOD-35732 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress