A genomic and evolutionary approach reveals non-genetic drug resistance in malaria.

ABSTRACT:

Background

Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated.

Results

We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid hom

SUBMITTER: Herman JD 

PROVIDER: S-EPMC4272547 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature