Adaptive Landscape by Environment Interactions Dictate Evolutionary Dynamics in Models of Drug Resistance.

ABSTRACT: The adaptive landscape analogy has found practical use in recent years, as many have explored how their understanding can inform therapeutic strategies that subvert the evolution of drug resistance. A major barrier to applications of these concepts is a lack of detail concerning how the environment affects adaptive landscape topography, and consequently, the outcome of drug treatment. Here we combine empirical data, evolutionary theory, and computer simulations towards dissecting adaptive landscape by environment interactions for the evolution of drug resistance in two dimensions-drug concentration and drug type. We do so by studying the resistance mediated by Plasmodium falciparum dihydrofolate reductase (DHFR) to two related inhibitors-pyrimethamine and cycloguanil-across a breadth of dr

SUBMITTER: Ogbunugafor CB 

PROVIDER: S-EPMC4726534 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature