Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.-- et al.

Detalles Bibliográficos
Autores: Rodríguez-Peña, José Manuel, Arroyo, Javier, Popolo, Laura
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/156934
Acceso en línea:http://hdl.handle.net/10261/156934
Access Level:acceso abierto
Palabra clave:MAP kinases
Cell integrity
Chitin
β(1,3)-glucan
Cell walls
Hyphal growth
Family GH72
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oai_identifier_str oai:digital.csic.es:10261/156934
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spelling Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodelingRodríguez-Peña, José ManuelArroyo, JavierPopolo, LauraMAP kinasesCell integrityChitinβ(1,3)-glucanCell wallsHyphal growthFamily GH72This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.-- et al.[Background]: The cell wall is essential for the yeast to hypha (Y-H) transition that enables Candida albicans to invade human tissues and evade the immune system. The main constituent, β(1,3)-glucan, is remodeled by glucanosyltransferases of the GH72 family. Phr1p is responsible of glucan remodeling at neutral-alkaline pH and is essential for morphogenesis and virulence. Due to the pH-regulated expression of PHR1, the phr1 phenotype is manifested at pH > 6 and its severity increases with the rise in pH. We exploited the pH-conditional nature of a PHR1 null mutant to analyze the impact of glucan remodeling on the hyphal transcriptional program and the role of chitin synthases in the hyphal wall stress (HWS) response. [Results]: In hyphal growth inducing conditions, phr1 germ tubes are defective in elongation, accumulate chitin, and constitutively activate the signaling pathways mediated by the MAP kinases Mkc1p, Cek1p and Hog1p. The transcriptional profiles revealed an increase of transcript levels for genes involved in cell wall formation (CHS2 and CHS8, CRH11, PGA23, orf19.750, RBR1, RBT4, ECM331, PGA6, PGA13), protein N-glycosylation and sorting in the ER (CWH8 and CHS7), signaling (CPP1, SSK2), ion transport (FLC2, YVC1), stress response and metabolism and a reduced expression of adhesins. A transient up-regulation of DNA replication genes associated with entry into S-phase occurred whereas cell-cycle regulating genes (PCL1, PCL2, CCN1, GIN4, DUN1, CDC28) were persistently up-regulated. To test the physiological relevance of altered CHS gene expression, phr1 chsx (x = 2,3,8) mutant phenotypes were analyzed during the Y-H transition. PHR1 deletion was synthetic lethal with CHS3 loss on solid M199 medium-pH 7.5 and with CHS8 deletion on solid M199-pH 8. On Spider medium, PHR1 was synthetic lethal with CHS3 or CHS8 at pH 8. [Conclusions]: The absence of Phr1p triggers an adaptive response aimed to reinforce the hyphal cell wall and restore homeostasis. Chs3p is essential in preserving phr1 cell integrity during the Y-H transition. Our findings also unveiled an unanticipated essential role of Chs8p during filamentation on solid media. These results highlight the flexibility of fungal cells in maintaining cell wall integrity and contribute to assessments of glucan remodeling as a target for therapy.This work was supported by the EU-RTN project “Cantrain” N.512481, FP 7 to L.P. and by grants BIO2013-48136-P (MINECO, Spain) and S2010/BDM-2414 (Comunidad de Madrid) to J.A. Collaboration between JA and LP was also supported by the ERASMUS Teaching mobility program between Universidad Complutense de Madrid and Università degli Studi di Milano.Peer ReviewedBioMed CentralUniversidad Complutense de MadridMinisterio de Economía y Competitividad (España)Comunidad de MadridUniversità degli Studi di MilanoEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720162017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/156934reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2013-48136-PS2010/BDM-2414/PROMPThttps://doi.org/10.1186/s12864-016-2853-5Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1569342026-05-22T06:33:51Z
dc.title.none.fl_str_mv Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
title Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
spellingShingle Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
Rodríguez-Peña, José Manuel
MAP kinases
Cell integrity
Chitin
β(1,3)-glucan
Cell walls
Hyphal growth
Family GH72
title_short Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
title_full Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
title_fullStr Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
title_full_unstemmed Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
title_sort Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking β(1,3)-glucan remodeling
dc.creator.none.fl_str_mv Rodríguez-Peña, José Manuel
Arroyo, Javier
Popolo, Laura
author Rodríguez-Peña, José Manuel
author_facet Rodríguez-Peña, José Manuel
Arroyo, Javier
Popolo, Laura
author_role author
author2 Arroyo, Javier
Popolo, Laura
author2_role author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
Ministerio de Economía y Competitividad (España)
Comunidad de Madrid
Università degli Studi di Milano
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv MAP kinases
Cell integrity
Chitin
β(1,3)-glucan
Cell walls
Hyphal growth
Family GH72
topic MAP kinases
Cell integrity
Chitin
β(1,3)-glucan
Cell walls
Hyphal growth
Family GH72
description This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.-- et al.
publishDate 2016
dc.date.none.fl_str_mv 2016
2017
2017
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/156934
url http://hdl.handle.net/10261/156934
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2013-48136-P
S2010/BDM-2414/PROMPT
https://doi.org/10.1186/s12864-016-2853-5

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instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
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