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

Kenthirapalan, S., Waters, A. P. , Matuschewski, K. and Kooij, T. W. A. (2016) Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite. Nature Communications, 7, 10519. (doi:10.1038/ncomms10519) (PMID:26796412) (PMCID:PMC4736113)

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Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Waters, Professor Andy
Authors: Kenthirapalan, S., Waters, A. P., Matuschewski, K., and Kooij, T. W. A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN:2041-1723
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2016 The Authors4
First Published:First published in Nature Communications 7:10519
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
466861Conditional translational repression: a core regulatory mechanism of gene expression during development of the malaria parasite.Andrew WatersWellcome Trust (WELLCOME)083811/Z/07/ZIII - PARASITOLOGY