The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum

A computer program that searches a genome database on the basis of the hydropathy plots of the corresponding proteins was used to identify more than 100 transport proteins encoded by P. falciparum. These include all the transporters previously annotated as such, as well as a similar number of candidate transport proteins that had escaped detection. Detailed sequence analysis enabled the assignment of putative substrate specificities and/or transport mechanisms to all those putative transport proteins previously without. The newly-identified transport proteins include candidate transporters for a range of organic and inorganic nutrients (including sugars, amino acids, nucleosides and vitamins), and several putative ion channels. The stage-dependent expression of RNAs for 34 candidate transport proteins of particular interest are compared.The malaria parasite possesses substantially more membrane transport proteins than was originally thought, and the analyses presented here provide a range of novel insights into the physiology of this important human pathogen.The malaria parasite (genus Plasmodium) is a unicellular eukaryote which, in the course of its complex life cycle, invades the erythrocytes of its vertebrate host. It is this intraerythrocytic phase of the parasite life cycle that gives rise to all the symptoms of malaria, a disease that is estimated to give rise to almost 5 billion episodes of clinical disease and up to 3 million deaths annually [1]. Plasmodium falciparum, the most virulent of the malaria parasites that infect humans, has developed resistance to most of the antimalarial drugs currently available. There is an urgent need for the development of new antimalarial drug strategies, and for an improved understanding of the mechanisms that underpin the parasite's ability to develop resistance to antimalarials.Membrane transport proteins are integral membrane proteins that mediate the translocation of molecules and ions across biological membranes. They