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A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites
Malaria parasites rely on a plastid organelle for survival during the blood stages of infection. However, the entire organelle is dispensable as long as the isoprenoid precursor, isopentenyl pyrophosphate (IPP), is supplemented in the culture medium. We engineered parasites to produce isoprenoid pre...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046295/ https://www.ncbi.nlm.nih.gov/pubmed/32059044 http://dx.doi.org/10.1371/journal.ppat.1008316 |
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author | Swift, Russell P. Rajaram, Krithika Liu, Hans B. Dziedzic, Amanda Jedlicka, Anne E. Roberts, Aleah D. Matthews, Krista A. Jhun, Hugo Bumpus, Namandje N. Tewari, Shivendra G. Wallqvist, Anders Prigge, Sean T. |
author_facet | Swift, Russell P. Rajaram, Krithika Liu, Hans B. Dziedzic, Amanda Jedlicka, Anne E. Roberts, Aleah D. Matthews, Krista A. Jhun, Hugo Bumpus, Namandje N. Tewari, Shivendra G. Wallqvist, Anders Prigge, Sean T. |
author_sort | Swift, Russell P. |
collection | PubMed |
description | Malaria parasites rely on a plastid organelle for survival during the blood stages of infection. However, the entire organelle is dispensable as long as the isoprenoid precursor, isopentenyl pyrophosphate (IPP), is supplemented in the culture medium. We engineered parasites to produce isoprenoid precursors from a mevalonate-dependent pathway, creating a parasite line that replicates normally after the loss of the apicoplast organelle. We show that carbon-labeled mevalonate is specifically incorporated into isoprenoid products, opening new avenues for researching this essential class of metabolites in malaria parasites. We also show that essential apicoplast proteins, such as the enzyme target of the drug fosmidomycin, can be deleted in this mevalonate bypass parasite line, providing a new method to determine the roles of other important apicoplast-resident proteins. Several antibacterial drugs kill malaria parasites by targeting basic processes, such as transcription, in the organelle. We used metabolomic and transcriptomic methods to characterize parasite metabolism after azithromycin treatment triggered loss of the apicoplast and found that parasite metabolism and the production of apicoplast proteins is largely unaltered. These results provide insight into the effects of apicoplast-disrupting drugs, several of which have been used to treat malaria infections in humans. Overall, the mevalonate bypass system provides a way to probe essential aspects of apicoplast biology and study the effects of drugs that target apicoplast processes. |
format | Online Article Text |
id | pubmed-7046295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-70462952020-03-09 A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites Swift, Russell P. Rajaram, Krithika Liu, Hans B. Dziedzic, Amanda Jedlicka, Anne E. Roberts, Aleah D. Matthews, Krista A. Jhun, Hugo Bumpus, Namandje N. Tewari, Shivendra G. Wallqvist, Anders Prigge, Sean T. PLoS Pathog Research Article Malaria parasites rely on a plastid organelle for survival during the blood stages of infection. However, the entire organelle is dispensable as long as the isoprenoid precursor, isopentenyl pyrophosphate (IPP), is supplemented in the culture medium. We engineered parasites to produce isoprenoid precursors from a mevalonate-dependent pathway, creating a parasite line that replicates normally after the loss of the apicoplast organelle. We show that carbon-labeled mevalonate is specifically incorporated into isoprenoid products, opening new avenues for researching this essential class of metabolites in malaria parasites. We also show that essential apicoplast proteins, such as the enzyme target of the drug fosmidomycin, can be deleted in this mevalonate bypass parasite line, providing a new method to determine the roles of other important apicoplast-resident proteins. Several antibacterial drugs kill malaria parasites by targeting basic processes, such as transcription, in the organelle. We used metabolomic and transcriptomic methods to characterize parasite metabolism after azithromycin treatment triggered loss of the apicoplast and found that parasite metabolism and the production of apicoplast proteins is largely unaltered. These results provide insight into the effects of apicoplast-disrupting drugs, several of which have been used to treat malaria infections in humans. Overall, the mevalonate bypass system provides a way to probe essential aspects of apicoplast biology and study the effects of drugs that target apicoplast processes. Public Library of Science 2020-02-14 /pmc/articles/PMC7046295/ /pubmed/32059044 http://dx.doi.org/10.1371/journal.ppat.1008316 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Swift, Russell P. Rajaram, Krithika Liu, Hans B. Dziedzic, Amanda Jedlicka, Anne E. Roberts, Aleah D. Matthews, Krista A. Jhun, Hugo Bumpus, Namandje N. Tewari, Shivendra G. Wallqvist, Anders Prigge, Sean T. A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites |
title | A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites |
title_full | A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites |
title_fullStr | A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites |
title_full_unstemmed | A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites |
title_short | A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites |
title_sort | mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046295/ https://www.ncbi.nlm.nih.gov/pubmed/32059044 http://dx.doi.org/10.1371/journal.ppat.1008316 |
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