Teaching old drugs new tricks to stop malaria invasion in its tracks

Abstract

Malaria is a common and life-threatening disease endemic in large parts of the world. The emergence of antimalarial drug resistance is threatening disease-control measures that depend heavily on treatment of clinical malaria. The intracellular malaria parasite is particularly vulnerable during its brief extracellular stage of the life cycle. Wilson et al. describe a screen targeting these extracellular parasite stages and make the surprising discovery that clinically used macrolide antibiotics are potent inhibitors of parasite invasion into erythrocytes.See research article: http://www.biomedcentral.com/1741-7007/13/52.

Fig. 1.

Two independent targets for macrolide antibiotics in Plasmodium falciparum. Azithromycin inhibits protein synthesis in the apicoplast (green). Loss of translation in the plastid ultimately starves the parasite (grey) for the essential isoprenoid precursor isopentenyl-pyrophosphate (IPP). Wilson et al. describe a second mode of action in which azithromycin blocks an early step in the process used by the parasite to invade red blood cells (RBC, red). This effect is much faster, but requires higher concentrations of drug