Plasmodium parasite exploits host aquaporin-3 during liver stage malaria infection

PLoS Pathogens
Dora PosfaiEmily R Derbyshire

Abstract

Within the liver a single Plasmodium parasite transforms into thousands of blood-infective forms to cause malaria. Here, we use RNA-sequencing to identify host genes that are upregulated upon Plasmodium berghei infection of hepatocytes with the hypothesis that host pathways are hijacked to benefit parasite development. We found that expression of aquaporin-3 (AQP3), a water and glycerol channel, is significantly induced in Plasmodium-infected hepatocytes compared to uninfected cells. This aquaglyceroporin localizes to the parasitophorous vacuole membrane, the compartmental interface between the host and pathogen, with a temporal pattern that correlates with the parasite's expansion in the liver. Depletion or elimination of host AQP3 expression significantly reduces P. berghei parasite burden during the liver stage and chemical disruption by a known AQP3 inhibitor, auphen, reduces P. falciparum asexual blood stage and P. berghei liver stage parasite load. Further use of this inhibitor as a chemical probe suggests that AQP3-mediated nutrient transport is an important function for parasite development. This study reveals a previously unknown potential route for host-dependent nutrient acquisition by Plasmodium which was discovered...Continue Reading

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Citations

Sep 26, 2019·Malaria Journal·Reto CaldelariVolker Heussler
Feb 6, 2020·MBio·Maria Toro-MorenoEmily R Derbyshire
Feb 16, 2021·Frontiers in Cellular and Infection Microbiology·Annemarie Voorberg-van der WelAnne-Marie Zeeman
Apr 25, 2020·Cell Chemical Biology·Dora PosfaiEmily R Derbyshire
Apr 2, 2021·PLoS Pathogens·Josh R Beck, Chi-Min Ho
Apr 3, 2021·Frontiers in Genetics·Abul Kalam AzadParveen Afroz Chowdhury
Jul 2, 2021·Frontiers in Cellular and Infection Microbiology·Kayla SylvesterEmily R Derbyshire
Jun 15, 2021·Bio-protocol·Annemarie Voorberg-van der WelClemens H M Kocken
Jul 17, 2021·Frontiers in Cellular and Infection Microbiology·Nadia AmanzougagheneJean-François Franetich
Oct 17, 2020·Drug Design, Development and Therapy·Tafere Mulaw Belete
Aug 11, 2021·Current Opinion in Microbiology·Matthias Garten, Josh R Beck
Jul 2, 2021·Chemical Reviews·Kamalakannan VijayanAlexis Kaushansky

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Methods Mentioned

BETA
RNA-seq
fluorescence-activated cell sorting
confocal microscopy
transfection
PCR
Fluorescent microscopy
PCA
NMR

Software Mentioned

Trimmomatic
DESeq2
MODEL
FastQC
STAR
SWISS
GSEA
R
Imaris

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