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Host biotin is required for liver stage development in malaria parasites

Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- a...

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Autores principales: Dellibovi-Ragheb, Teegan A., Jhun, Hugo, Goodman, Christopher D., Walters, Maroya S., Ragheb, Daniel R. T., Matthews, Krista A., Rajaram, Krithika, Mishra, Satish, McFadden, Geoffrey I., Sinnis, Photini, Prigge, Sean T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856565/
https://www.ncbi.nlm.nih.gov/pubmed/29483266
http://dx.doi.org/10.1073/pnas.1800717115
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author Dellibovi-Ragheb, Teegan A.
Jhun, Hugo
Goodman, Christopher D.
Walters, Maroya S.
Ragheb, Daniel R. T.
Matthews, Krista A.
Rajaram, Krithika
Mishra, Satish
McFadden, Geoffrey I.
Sinnis, Photini
Prigge, Sean T.
author_facet Dellibovi-Ragheb, Teegan A.
Jhun, Hugo
Goodman, Christopher D.
Walters, Maroya S.
Ragheb, Daniel R. T.
Matthews, Krista A.
Rajaram, Krithika
Mishra, Satish
McFadden, Geoffrey I.
Sinnis, Photini
Prigge, Sean T.
author_sort Dellibovi-Ragheb, Teegan A.
collection PubMed
description Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- and blood-stage malaria parasites; however, it is activated through biotinylation only in the liver stages. Consistent with this observation, deletion of the biotin ligase responsible for ACC biotinylation does not impede blood-stage growth, but results in late liver-stage developmental defects. Biotin depletion increases the severity of the developmental defects, demonstrating that parasite and host biotin metabolism are required for normal liver-stage progression. This finding may link the development of liver-stage malaria parasites to the nutritional status of the host, as neither the parasite nor the human host can synthesize biotin.
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spelling pubmed-58565652018-04-05 Host biotin is required for liver stage development in malaria parasites Dellibovi-Ragheb, Teegan A. Jhun, Hugo Goodman, Christopher D. Walters, Maroya S. Ragheb, Daniel R. T. Matthews, Krista A. Rajaram, Krithika Mishra, Satish McFadden, Geoffrey I. Sinnis, Photini Prigge, Sean T. Proc Natl Acad Sci U S A PNAS Plus Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- and blood-stage malaria parasites; however, it is activated through biotinylation only in the liver stages. Consistent with this observation, deletion of the biotin ligase responsible for ACC biotinylation does not impede blood-stage growth, but results in late liver-stage developmental defects. Biotin depletion increases the severity of the developmental defects, demonstrating that parasite and host biotin metabolism are required for normal liver-stage progression. This finding may link the development of liver-stage malaria parasites to the nutritional status of the host, as neither the parasite nor the human host can synthesize biotin. National Academy of Sciences 2018-03-13 2018-02-26 /pmc/articles/PMC5856565/ /pubmed/29483266 http://dx.doi.org/10.1073/pnas.1800717115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Dellibovi-Ragheb, Teegan A.
Jhun, Hugo
Goodman, Christopher D.
Walters, Maroya S.
Ragheb, Daniel R. T.
Matthews, Krista A.
Rajaram, Krithika
Mishra, Satish
McFadden, Geoffrey I.
Sinnis, Photini
Prigge, Sean T.
Host biotin is required for liver stage development in malaria parasites
title Host biotin is required for liver stage development in malaria parasites
title_full Host biotin is required for liver stage development in malaria parasites
title_fullStr Host biotin is required for liver stage development in malaria parasites
title_full_unstemmed Host biotin is required for liver stage development in malaria parasites
title_short Host biotin is required for liver stage development in malaria parasites
title_sort host biotin is required for liver stage development in malaria parasites
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856565/
https://www.ncbi.nlm.nih.gov/pubmed/29483266
http://dx.doi.org/10.1073/pnas.1800717115
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