Atovaquone Tolerance in Plasmodium Falciparum Parasites Selected for High-level Resistance to a Dihydroorotate Dehydrogenase Inhibitor

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2014 Oct 22

PMID 25331708

Citations 10

Authors

Jennifer L Guler

John White 3rd

Margaret A Phillips

Pradipsinh K Rathod

Affiliations

Soon will be listed here.

Abstract

Atovaquone is a component of Malarone, a widely prescribed antimalarial combination, that targets malaria respiration. Here we show that parasites with high-level resistance to an inhibitor of dihydroorotate dehydrogenase demonstrate unexpected atovaquone tolerance. Fortunately, the tolerance is diminished with proguanil, the second partner in Malarone. It is important to understand such "genetic cross talk" between respiration and pyrimidine biosynthesis since many antimalarial drug development programs target these two seemingly independent pathways.

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