title: Targeting Protein Translation in Organelles of the Apicomplexa.
abstract: Antibiotics inhibiting protein translation have long been used to treat and prevent infections by apicomplexan parasites. These compounds kill parasites by inhibiting organellar translation, and most act specifically against the apicoplast, a relict plastid in apicomplexans. Drug resistance in Plasmodium and other apicomplexans dictates a need for development of novel targets. Some apicoplast inhibitors have a delayed onset of action, so they cannot replace fast-acting drugs, although they still fulfil important roles in treating and preventing infections. The plethora of bacterial-like actors in the translation machinery of parasite mitochondria and plastids presents validated targets with strong potential for selectivity. Here we discuss existing drugs that inhibit organellar translation, and explore targets that may be further exploited in antiparasitic drug design.
authors: School of Biosciences, The University of Melbourne, Melbourne, Victoria 3010, Australia.
authors: Christopher D
authors: CD
authors: Goodman
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
authors: Charisse Flerida A
authors: CFA
authors: Pasaje
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
authors: Kit
authors: K
authors: Kennedy
authors: School of Biosciences, The University of Melbourne, Melbourne, Victoria 3010, Australia.
authors: Geoffrey I
authors: GI
authors: McFadden
authors: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia. Electronic address: saralph@unimelb.edu.au.
authors: Stuart A
authors: SA
authors: Ralph
mesh_terms: D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use; D016782:Apicomplexa / Q000187:drug effects* / Q000235:genetics*; D063546:Apicoplasts / Q000187:drug effects / Q000235:genetics*; D004351:Drug Resistance / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics*; D014176:Protein Biosynthesis / Q000187:drug effects
chemical_list: D000981:Antiprotozoal Agents
keywords: Plasmodium; Toxoplasma; apicoplast; mitochondrion; protein translation; ribosome