Selective inhibition of apicoplast tryptophanyl-tRNA synthetase causes delayed death in Plasmodium falciparum

• DOI: 10.1038/srep27531
• Publication Date: 2016-06-09T09:36:39Z
• Authors: Charisse Flerida ...; Vanessa Cheung; Kit Kennedy; Erin E. Lim; Jonathan B. Baell; Michael D. W. Gri...; Stuart A. Ralph
• Keywords: Apicoplast; Plasmodium berghei; Isopentenyl pyrophosphate; Aminoacylation

Abstract The malaria parasite Plasmodium falciparum relies on efficient protein translation. An essential component of translation is the tryptophanyl-tRNA synthetase (TrpRS) that charges tRNA trp . Here we characterise two isoforms TrpRS in Plasmodium; one eukaryotic type localises to cytosol and a bacterial remnant plastid (apicoplast). We show apicoplast aminoacylates while cytosolic inhibitor TrpRSs, indolmycin, specifically inhibits aminoacylation by vitro , ex vivo growth, killing parasites with delayed death effect characteristic inhibitors. Indolmycin treatment ablates inheritance rescuable addition metabolite isopentenyl pyrophosphate (IPP). These data establish inhibition an housekeeping enzyme leads loss this sufficient for death. Apicoplast promising, specific antimalarial target.