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

Nature Communications
Sanketha KenthirapalanTaco W A Kooij

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.

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Citations

Dec 22, 2017·Open Biology·David A BakerEloise M Walker
May 9, 2018·Molecular Microbiology·Pierre-Mehdi HammoudiDominique Soldati-Favre
Sep 20, 2019·Science Translational Medicine·Joost SchalkwijkKoen J Dechering
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Dec 22, 2017·Emerging Topics in Life Sciences·Henry M StainesSanjeev Krishna
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Mar 20, 2020·Trends in Parasitology·Özlem Günay-Esiyok, Nishith Gupta
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Dec 31, 2021·PLoS Pathogens·Laura E de VriesDominique Soldati-Favre

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Methods Mentioned

BETA
transfection
flow cytometry
genotyping
PCR

Software Mentioned

Fiji

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