Fitness trade-offs in the evolution of dihydrofolate reductase and drug resistance in Plasmodium falciparum.

ABSTRACT:

Background

Patterns of emerging drug resistance reflect the underlying adaptive landscapes for specific drugs. In Plasmodium falciparum, the parasite that causes the most serious form of malaria, antifolate drugs inhibit the function of essential enzymes in the folate pathway. However, a handful of mutations in the gene coding for one such enzyme, dihydrofolate reductase, confer drug resistance. Understanding how evolution proceeds from drug susceptibility to drug resistance is critical if new antifolate treatments are to have sustained usefulness.

Methodology/principal findings

We use a transgenic yeast expression system to build on previous studies that described the adaptive landscape for the antifolate drug pyrimethamine, and we describe the most likely evolutionary traj

SUBMITTER: Costanzo MS 

PROVIDER: S-EPMC3100297 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature