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Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network

Biofilms of the fungal pathogen Candida albicans include abundant long filaments called hyphae. These cells express hypha-associated genes, which specify diverse virulence functions including surface adhesins that ensure biofilm integrity. Biofilm formation, virulence, and hypha-associated gene expr...

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Autores principales: Cravener, Max V., Do, Eunsoo, May, Gemma, Zarnowski, Robert, Andes, David R., McManus, C. Joel, Mitchell, Aaron P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901766/
https://www.ncbi.nlm.nih.gov/pubmed/36696432
http://dx.doi.org/10.1371/journal.ppat.1011109
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author Cravener, Max V.
Do, Eunsoo
May, Gemma
Zarnowski, Robert
Andes, David R.
McManus, C. Joel
Mitchell, Aaron P.
author_facet Cravener, Max V.
Do, Eunsoo
May, Gemma
Zarnowski, Robert
Andes, David R.
McManus, C. Joel
Mitchell, Aaron P.
author_sort Cravener, Max V.
collection PubMed
description Biofilms of the fungal pathogen Candida albicans include abundant long filaments called hyphae. These cells express hypha-associated genes, which specify diverse virulence functions including surface adhesins that ensure biofilm integrity. Biofilm formation, virulence, and hypha-associated gene expression all depend upon the transcription factor Efg1. This transcription factor has been characterized extensively in the C. albicans type strain SC5314 and derivatives, but only recently has its function been explored in other clinical isolates. Here we define a principal set of Efg1-responsive genes whose expression is significantly altered by an efg1Δ/Δ mutation across 17 clinical isolates. This principal gene set includes 68 direct Efg1 targets, whose 5’ regions are bound by Efg1 in five clinical isolates, and 42 indirect Efg1 targets, whose 5’ regions are not detectably bound by Efg1. Three direct Efg1 target genes encode transcription factors—BRG1, UME6, and WOR3 –whose increased expression in an efg1Δ/Δ mutant restores expression of multiple indirect and direct principal targets, as well as biofilm formation ability. Although BRG1 and UME6 are well known positive regulators of hypha-associated genes and biofilm formation, WOR3 is best known as an antagonist of Efg1 in the sexual mating pathway. We confirm the positive role of WOR3 in biofilm formation with the finding that a wor3Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo biofilm model. Positive control of Efg1 direct target genes by other Efg1 direct target genes–BRG1, UME6, and WOR3 –may buffer principal Efg1-responsive gene expression against the impact of genetic variation in the C. albicans species.
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spelling pubmed-99017662023-02-07 Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network Cravener, Max V. Do, Eunsoo May, Gemma Zarnowski, Robert Andes, David R. McManus, C. Joel Mitchell, Aaron P. PLoS Pathog Research Article Biofilms of the fungal pathogen Candida albicans include abundant long filaments called hyphae. These cells express hypha-associated genes, which specify diverse virulence functions including surface adhesins that ensure biofilm integrity. Biofilm formation, virulence, and hypha-associated gene expression all depend upon the transcription factor Efg1. This transcription factor has been characterized extensively in the C. albicans type strain SC5314 and derivatives, but only recently has its function been explored in other clinical isolates. Here we define a principal set of Efg1-responsive genes whose expression is significantly altered by an efg1Δ/Δ mutation across 17 clinical isolates. This principal gene set includes 68 direct Efg1 targets, whose 5’ regions are bound by Efg1 in five clinical isolates, and 42 indirect Efg1 targets, whose 5’ regions are not detectably bound by Efg1. Three direct Efg1 target genes encode transcription factors—BRG1, UME6, and WOR3 –whose increased expression in an efg1Δ/Δ mutant restores expression of multiple indirect and direct principal targets, as well as biofilm formation ability. Although BRG1 and UME6 are well known positive regulators of hypha-associated genes and biofilm formation, WOR3 is best known as an antagonist of Efg1 in the sexual mating pathway. We confirm the positive role of WOR3 in biofilm formation with the finding that a wor3Δ/Δ mutation impairs biofilm formation in vitro and in an in vivo biofilm model. Positive control of Efg1 direct target genes by other Efg1 direct target genes–BRG1, UME6, and WOR3 –may buffer principal Efg1-responsive gene expression against the impact of genetic variation in the C. albicans species. Public Library of Science 2023-01-25 /pmc/articles/PMC9901766/ /pubmed/36696432 http://dx.doi.org/10.1371/journal.ppat.1011109 Text en © 2023 Cravener et al 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 the original author and source are credited.
spellingShingle Research Article
Cravener, Max V.
Do, Eunsoo
May, Gemma
Zarnowski, Robert
Andes, David R.
McManus, C. Joel
Mitchell, Aaron P.
Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network
title Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network
title_full Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network
title_fullStr Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network
title_full_unstemmed Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network
title_short Reinforcement amid genetic diversity in the Candida albicans biofilm regulatory network
title_sort reinforcement amid genetic diversity in the candida albicans biofilm regulatory network
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9901766/
https://www.ncbi.nlm.nih.gov/pubmed/36696432
http://dx.doi.org/10.1371/journal.ppat.1011109
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