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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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Autores principales: Glittenberg, Marcus T., Kounatidis, Ilias, Atilano, Magda, Ligoxygakis, Petros
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118035/
https://www.ncbi.nlm.nih.gov/pubmed/35142345
http://dx.doi.org/10.1242/dmm.049218
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author Glittenberg, Marcus T.
Kounatidis, Ilias
Atilano, Magda
Ligoxygakis, Petros
author_facet Glittenberg, Marcus T.
Kounatidis, Ilias
Atilano, Magda
Ligoxygakis, Petros
author_sort Glittenberg, Marcus T.
collection PubMed
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 pubmed-91180352022-05-19 A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection Glittenberg, Marcus T. Kounatidis, Ilias Atilano, Magda Ligoxygakis, Petros Dis Model Mech Research Article 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. The Company of Biologists Ltd 2022-05-09 /pmc/articles/PMC9118035/ /pubmed/35142345 http://dx.doi.org/10.1242/dmm.049218 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Glittenberg, Marcus T.
Kounatidis, Ilias
Atilano, Magda
Ligoxygakis, Petros
A genetic screen in Drosophila reveals the role of fucosylation in host susceptibility to Candida infection
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 Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118035/
https://www.ncbi.nlm.nih.gov/pubmed/35142345
http://dx.doi.org/10.1242/dmm.049218
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