Atovaquone Tolerance in Plasmodium falciparum Parasites Selected for High-Level Resistance to a Dihydroorotate Dehydrogenase Inhibitor

作者:Guler Jennifer L; White John III; Phillips Margaret A; Rathod Pradipsinh K*
来源:Antimicrobial Agents and Chemotherapy, 2015, 59(1): 686-689.
DOI:10.1128/AAC.02347-14

摘要

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.

  • 出版日期2015-1