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Content Provider | PubMed Central |
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Author | Pasaje, Charisse Flerida A. Cheung, Vanessa Kennedy, Kit Lim, Erin E. Baell, Jonathan B. Griffin, Michael D. W. Ralph, Stuart A. |
Copyright Year | 2016 |
Abstract | The malaria parasite Plasmodium falciparum relies on efficient protein translation. An essential component of translation is the tryptophanyl-tRNA synthetase (TrpRS) that charges tRNAtrp. Here we characterise two isoforms of TrpRS in Plasmodium; one eukaryotic type localises to the cytosol and a bacterial type localises to the remnant plastid (apicoplast). We show that the apicoplast TrpRS aminoacylates bacterial tRNAtrp while the cytosolic TrpRS charges eukaryotic tRNAtrp. An inhibitor of bacterial TrpRSs, indolmycin, specifically inhibits aminoacylation by the apicoplast TrpRS in vitro, and inhibits ex vivo Plasmodium parasite growth, killing parasites with a delayed death effect characteristic of apicoplast inhibitors. Indolmycin treatment ablates apicoplast inheritance and is rescuable by addition of the apicoplast metabolite isopentenyl pyrophosphate (IPP). These data establish that inhibition of an apicoplast housekeeping enzyme leads to loss of the apicoplast and this is sufficient for delayed death. Apicoplast TrpRS is essential for protein translation and is a promising, specific antimalarial target. |
Related Links | http://dx.doi.org/10.1038/srep27531 |
Starting Page | 27531 |
File Format | |
ISSN | 20452322 |
e-ISSN | 20452322 |
Journal | Scientific Reports |
Volume Number | 6 |
Language | English |
Publisher | Nature Publishing Group |
Publisher Date | 2016-06-01 |
Access Restriction | Open |
Rights Holder | Nature Publishing Group |
Subject Keyword | Science and technology Research in Higher Education |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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