Atovaquone resistance in malaria parasites

Abstract

Atovaquone is a broad-spectrum antiparasitic agent active against malaria, Pneumocystis carinii pneumonia, toxoplasmosis and babesiosis. When used as a single agent, resistance to atovaquone arose rapidly in falciparum malaria, requiring the development of a new antimalarial drug combination of atovaquone and proguanil. Recent laboratory investigations have provided insights into the mode of atovaquone action, and identified the molecular basis for the resistance development. Mutations within a catalytic domain of the cytochrome bc1 complex present within the parasite mitochondrial inner membrane were shown to be responsible for atovaquone resistance. Here, we review these studies and propose a mechanism by which atovaquone resistance may arise quickly in malaria parasites. (C) 2000 Harcourt Publishers Ltd.