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

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  • Sanketha Kenthirapalan

    (Parasitology Unit, Max Planck Institute for Infection Biology)

  • Andrew P. Waters

    (Wellcome Trust Centre for Molecular Parasitology, Glasgow Biomedical Research Centre, University of Glasgow)

  • Kai Matuschewski

    (Parasitology Unit, Max Planck Institute for Infection Biology
    Institute of Biology, Humboldt University)

  • Taco W. A. Kooij

    (Parasitology Unit, Max Planck Institute for Infection Biology
    Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre
    Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre)

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.

Suggested Citation

  • Sanketha Kenthirapalan & Andrew P. Waters & Kai Matuschewski & Taco W. A. Kooij, 2016. "Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10519
    DOI: 10.1038/ncomms10519
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