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)

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 > School of Infection & Immunity
• 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

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
46686	1	Conditional translational repression: a core regulatory mechanism of gene expression during development of the malaria parasite.	Andrew Waters	Wellcome Trust (WELLCOME)	083811/Z/07/Z	III - PARASITOLOGY