UDP-galactose and acetyl-CoA transporters as Plasmodium multidrug resistance genes.

A molecular understanding of drug resistance mechanisms enables surveillance of the effectiveness of new antimicrobial therapies during development and deployment in the field. We used conventional drug resistance selection as well as a regime of limiting dilution at early stages of drug treatment to probe two antimalarial imidazolopiperazines, KAF156 and GNF179. The latter approach permits the isolation of low-fitness mutants that might otherwise be out-competed during selection.

Targeting of a Transporter to the Outer Apicoplast Membrane in the Human Malaria Parasite Plasmodium falciparum.

Apicoplasts are vestigial plastids in apicomplexan parasites like Plasmodium, the causative agent of malaria. Apicomplexan parasites are dependant on their apicoplasts for synthesis of various molecules that they are unable to scavenge in sufficient quantity from their host, which makes apicoplasts attractive drug targets. Proteins known as plastid phosphate translocators (pPTs) are embedded in the outer apicoplast membrane and are responsible for the import of carbon, energy and reducing power to drive anabolic synthesis in the organelle.

The evolution, metabolism and functions of the apicoplast.

The malaria parasite, Plasmodium falciparum, harbours a relict plastid known as the 'apicoplast'. The discovery of the apicoplast ushered in an exciting new prospect for drug development against the parasite. The eubacterial ancestry of the organelle offers a wealth of opportunities for the development of therapeutic interventions.

The carbon and energy sources of the non-photosynthetic plastid in the malaria parasite.

The malaria parasite harbours an indispensable plastid known as the 'apicoplast'. The apicoplast's exact role remains uncertain, but it houses components involved in fatty acid, isoprenoid and haem biosyntheses. These pathways offer opportunities to develop anti-malarials.

New proteins in the apicoplast membranes: time to rethink apicoplast protein targeting.

Several apicomplexan parasites harbour an essential plastid known as the apicoplast. Apicoplasts import proteins and metabolites for several biological functions, but how import is achieved is largely unknown. Two recent reports have identified novel proteins in the apicoplast membranes, providing new perspectives on how proteins traffic to this organelle.

Membrane transporters in the relict plastid of malaria parasites.

Malaria parasites contain a nonphotosynthetic plastid homologous to chloroplasts of plants. The parasite plastid synthesizes fatty acids, heme, iron sulfur clusters and isoprenoid precursors and is indispensable, making it an attractive target for antiparasite drugs. How parasite plastid biosynthetic pathways are fuelled in the absence of photosynthetic capture of energy and carbon was not clear.