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Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite

Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of...

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Autores principales: Kenthirapalan, Sanketha, Waters, Andrew P., Matuschewski, Kai, Kooij, Taco W. A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736113/
https://www.ncbi.nlm.nih.gov/pubmed/26796412
http://dx.doi.org/10.1038/ncomms10519
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author Kenthirapalan, Sanketha
Waters, Andrew P.
Matuschewski, Kai
Kooij, Taco W. A.
author_facet Kenthirapalan, Sanketha
Waters, Andrew P.
Matuschewski, Kai
Kooij, Taco W. A.
author_sort Kenthirapalan, Sanketha
collection PubMed
description Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria.
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spelling pubmed-47361132016-03-04 Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite Kenthirapalan, Sanketha Waters, Andrew P. Matuschewski, Kai Kooij, Taco W. A. Nat Commun Article Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria. Nature Publishing Group 2016-01-22 /pmc/articles/PMC4736113/ /pubmed/26796412 http://dx.doi.org/10.1038/ncomms10519 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Kenthirapalan, Sanketha
Waters, Andrew P.
Matuschewski, Kai
Kooij, Taco W. A.
Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
title Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
title_full Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
title_fullStr Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
title_full_unstemmed Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
title_short Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
title_sort functional profiles of orphan membrane transporters in the life cycle of the malaria parasite
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736113/
https://www.ncbi.nlm.nih.gov/pubmed/26796412
http://dx.doi.org/10.1038/ncomms10519
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