Parasite plastids: approaching the endgame.
Considerable work still needs to be done to understand more fully the basic processes going on inside the non-photosynthetic plastid organelle of Plasmodium spp., the causative agent of malaria. Following an explosion of genomic and transcriptional information in recent years, research workers are still analysing these data looking for new material relevant to the plastid. Several metabolic and housekeeping functions based on bacterial biochemistry have been elucidated and this has given impetus to finding lead inhibitors based on established anti-microbials. Structural investigations of plastid-associated enzymes identified as potential targets have begun. This review gives a perspective on the research to date and hopes to emphasize that a practical outcome for the clinic should be an important focus of future efforts. Malaria parasites have become resistant to front-line anti-malarials that are widely used and were formerly dependable. This has become a worrying problem in many regions where malaria is endemic. The time lag between hunting for new inhibitors and their application as pharmaceuticals is so long and costly that a steady stream of new ventures has to be undertaken to give a reasonable chance of finding affordable and appropriate anti-malarials for the future. Attempts to find inhibitors of the plastid organelle of the malaria parasite should be intensified in such programmes.
Wilson
R J M Iain
RJ
National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK. rwilson@nimr.mrc.ac.uk
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D005075:Biological Evolution; D018503:Genome, Protozoan; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D015388:Organelles / Q000378:metabolism; D021261:Parasitic Sensitivity Tests; D010802:Phylogeny; D010961:Plasmodium / Q000145:classification / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D018087:Plastids / Q000378:metabolism*
D000962:Antimalarials