title: Characterization of two malaria parasite organelle translation elongation factor G proteins: the likely targets of the anti-malarial fusidic acid.
abstract: Malaria parasites harbour two organelles with bacteria-like metabolic processes that are the targets of many anti-bacterial drugs. One such drug is fusidic acid, which inhibits the translation component elongation factor G. The response of P. falciparum to fusidic acid was characterised using extended SYBR-Green based drug trials. This revealed that fusidic acid kills in vitro cultured P. falciparum parasites by immediately blocking parasite development. Two bacterial-type protein translation elongation factor G genes are identified as likely targets of fusidic acid. Sequence analysis suggests that these proteins function in the mitochondria and apicoplast and both should be sensitive to fusidic acid. Microscopic examination of protein-reporter fusions confirm the prediction that one elongation factor G is a component of parasite mitochondria whereas the second is a component of the relict plastid or apicoplast. The presence of two putative targets for a single inhibitory compound emphasizes the potential of elongation factor G as a drug target in malaria.
authors.affiliation: Plant Cell Biology Research Centre-School of Botany, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Russell A
authors.initials: RA
authors.lastname: Johnson
authors.forename: Geoffrey I
authors.initials: GI
authors.lastname: McFadden
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Goodman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D019295:Computational Biology; D005672:Fusidic Acid / Q000494:pharmacology*; D008018:Life Cycle Stages / Q000187:drug effects; D008288:Malaria / Q000469:parasitology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D015388:Organelles / Q000187:drug effects / Q000378:metabolism*; D010271:Parasites / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D020653:Peptide Elongation Factor G / Q000737:chemistry / Q000378:metabolism*; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D014176:Protein Biosynthesis / Q000187:drug effects*; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D024101:Mitochondrial Proteins; D020653:Peptide Elongation Factor G; D015800:Protozoan Proteins; D005672:Fusidic Acid