Copper-transporting ATPase is important for malaria parasite fertility

Kenthirapalan, S., Waters, A. P. , Matuschewski, K. and Kooij, T. W. A. (2014) Copper-transporting ATPase is important for malaria parasite fertility. Molecular Microbiology, 91(2), pp. 315-325. (doi: 10.1111/mmi.12461)

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Homeostasis of the trace element copper is essential to all eukaryotic life. Copper serves as a cofactor in metalloenzymes and catalyses electron transfer reactions as well as the generation of potentially toxic reactive oxygen species. Here, we describe the functional characterization of an evolutionarily highly conserved, predicted copper-transporting P-type ATPase (CuTP) in the murine malaria model parasite Plasmodium berghei. Live imaging of a parasite line expressing a fluorescently tagged CuTP demonstrated that CuTP is predominantly located in vesicular bodies of the parasite. A P. berghei loss-of-function mutant line was readily obtained and showed no apparent defect in in vivo blood stage growth. Parasite transmission through the mosquito vector was severely affected, but not entirely abolished. We show that male and female gametocytes are abundant in cutp− parasites, but activation of male microgametes and exflagellation were strongly impaired. This specific defect could be mimicked by addition of the copper chelator neocuproine to wild-type gametocytes. A cross-fertilization assay demonstrated that female fertility was also severely abrogated. In conclusion, we provide experimental genetic and pharmacological evidence that a healthy copper homeostasis is critical to malaria parasite fertility of both genders of gametocyte and, hence, to transmission to the mosquito vector.

Item Type:Articles
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:Molecular Microbiology
Publisher:Wiley-Blackwell Publishing Ltd
ISSN (Online):1365-2958
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Molecular Microbiology 91(2):315-325
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