A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection

Candida infections constitute a blind spot in global public health as very few new anti-fungal drugs are being developed. Genetic surveys of host susceptibilities to such infections using mammalian models have certain disadvantages in that obtaining results is time-consuming, owing to relatively lon...

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Main Authors: Marcus T. Glittenberg, Ilias Kounatidis, Magda Atilano, Petros Ligoxygakis
Format: Article
Language:English
Published: The Company of Biologists 2022-05-01
Series:Disease Models & Mechanisms
Subjects:
Online Access:http://dmm.biologists.org/content/15/5/dmm049218
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author Marcus T. Glittenberg
Ilias Kounatidis
Magda Atilano
Petros Ligoxygakis
author_facet Marcus T. Glittenberg
Ilias Kounatidis
Magda Atilano
Petros Ligoxygakis
author_sort Marcus T. Glittenberg
collection DOAJ
description Candida infections constitute a blind spot in global public health as very few new anti-fungal drugs are being developed. Genetic surveys of host susceptibilities to such infections using mammalian models have certain disadvantages in that obtaining results is time-consuming, owing to relatively long lifespans, and these results have low statistical resolution because sample sizes are usually small. Here, we report a targeted genetic screening of 5698 RNAi lines encompassing 4135 Drosophila genes with human homologues, several of which we identify as important for host survival after Candida albicans infection. These include genes in a variety of functional classes encompassing gene expression, intracellular signalling, metabolism and enzymatic regulation. Analysis of one of the screen hits, the infection-induced α-(1,3)-fucosylase FucTA, showed that N-glycan fucosylation has several targets among proteins involved in host defence, which provides multiple avenues of investigation for the mechanistic analysis of host survival to systemic C. albicans infection.
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spelling doaj.art-01fc659659754cc6a058e1a36ce55ef62022-12-22T00:32:35ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112022-05-0115510.1242/dmm.049218049218A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infectionMarcus T. Glittenberg0Ilias Kounatidis1Magda Atilano2Petros Ligoxygakis3 Department of Biochemistry, University of Oxford, South Parks Rd, Oxford OX1 3QU, UK Department of Biochemistry, University of Oxford, South Parks Rd, Oxford OX1 3QU, UK Department of Biochemistry, University of Oxford, South Parks Rd, Oxford OX1 3QU, UK Department of Biochemistry, University of Oxford, South Parks Rd, Oxford OX1 3QU, UK Candida infections constitute a blind spot in global public health as very few new anti-fungal drugs are being developed. Genetic surveys of host susceptibilities to such infections using mammalian models have certain disadvantages in that obtaining results is time-consuming, owing to relatively long lifespans, and these results have low statistical resolution because sample sizes are usually small. Here, we report a targeted genetic screening of 5698 RNAi lines encompassing 4135 Drosophila genes with human homologues, several of which we identify as important for host survival after Candida albicans infection. These include genes in a variety of functional classes encompassing gene expression, intracellular signalling, metabolism and enzymatic regulation. Analysis of one of the screen hits, the infection-induced α-(1,3)-fucosylase FucTA, showed that N-glycan fucosylation has several targets among proteins involved in host defence, which provides multiple avenues of investigation for the mechanistic analysis of host survival to systemic C. albicans infection.http://dmm.biologists.org/content/15/5/dmm049218candida albicansdrosophilagenetic screenfucosylationhost-pathogen interaction
spellingShingle Marcus T. Glittenberg
Ilias Kounatidis
Magda Atilano
Petros Ligoxygakis
A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
Disease Models & Mechanisms
candida albicans
drosophila
genetic screen
fucosylation
host-pathogen interaction
title A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
title_full A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
title_fullStr A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
title_full_unstemmed A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
title_short A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
title_sort genetic screen in drosophila reveals the role of fucosylation in host susceptibility to candida infection
topic candida albicans
drosophila
genetic screen
fucosylation
host-pathogen interaction
url http://dmm.biologists.org/content/15/5/dmm049218
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