PfCRT-mediated drug transport in malarial parasites

Abstract

A wide range of drug transport studies using intact infected red blood cells, isolated malarial parasites, heterologous expression systems, and purified protein, combined with elegant genetic experiments, have suggested that chloroquine transport by the Plasmodium falciparum chloroquine resistance transporter (PfCRT) is a key aspect of the molecular mechanism of quinoline antimalarial drug resistance. However, many questions remain. This short review summarizes data that have led to drug channel versus drug pump hypotheses for PfCRT and suggests ways in which recent contrasting interpretations might be reconciled.

Figure

Schematic of PfCRT protein generated using TMRPres2D (http://bioinformatics.biol.uoa.gr/TMRPres2D/index.jsp). Vertical arrow indicates the covalent attachment site of the terminal domain of a CQ photoaffinity probe [62]. Dashed boxes (horizontal arrows) denote the proposed binding site of the chloroquine quinolinal ring system, based on photolabelling data and mass spectrometry (see [62]).