Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature

[Background]: The fungal cell wall forms a compact network whose integrity is essential for cell morphology and viability. Thus, fungal cells have evolved mechanisms to elicit adequate adaptive responses when cell wall integrity (CWI) is compromised. Functional genomic approaches provide a unique op...

Descripción completa

Detalles Bibliográficos
Autores: García, Raúl, Botet, Javier, Rodríguez-Peña, José Manuel, Bermejo, Clara, Ribas, Juan Carlos, Revuelta Doval, José Luis, Nombela, César, Arroyo, Javier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/156881
Acceso en línea:http://hdl.handle.net/10261/156881
Access Level:acceso abierto
Palabra clave:Genomics
Chitin
β-1,3 glucan
Screening
Cell integrity
Fungal cell wall
id ES_40effbb1ef08ce278bfccc6d5eb184b5
oai_identifier_str oai:digital.csic.es:10261/156881
network_acronym_str ES
network_name_str España
repository_id_str
spelling Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signatureGarcía, RaúlBotet, JavierRodríguez-Peña, José ManuelBermejo, ClaraRibas, Juan CarlosRevuelta Doval, José LuisNombela, CésarArroyo, JavierGenomicsChitinβ-1,3 glucanScreeningCell integrityFungal cell wall[Background]: The fungal cell wall forms a compact network whose integrity is essential for cell morphology and viability. Thus, fungal cells have evolved mechanisms to elicit adequate adaptive responses when cell wall integrity (CWI) is compromised. Functional genomic approaches provide a unique opportunity to globally characterize these adaptive mechanisms. To provide a global perspective on these CWI regulatory mechanisms, we developed chemical-genomic profiling of haploid mutant budding yeast cells to systematically identify in parallel those genes required to cope with stresses interfering the cell wall by different modes of action: β-1,3 glucanase and chitinase activities (zymolyase), inhibition of β-1,3 glucan synthase (caspofungin) and binding to chitin (Congo red). [Results]: Measurement of the relative fitness of the whole collection of 4786 haploid budding yeast knock-out mutants identified 222 mutants hypersensitive to caspofungin, 154 mutants hypersensitive to zymolyase, and 446 mutants hypersensitive to Congo red. Functional profiling uncovered both common and specific requirements to cope with different cell wall damages. We identified a cluster of 43 genes highly important for the integrity of the cell wall as the common >signature of cell wall maintenance (CWM)>. This cluster was enriched in genes related to vesicular trafficking and transport, cell wall remodeling and morphogenesis, transcription and chromatin remodeling, signal transduction and RNA metabolism. Although the CWI pathway is the main MAPK pathway regulating cell wall integrity, the collaboration with other signal transduction pathways like the HOG pathway and the invasive growth pathway is also required to cope with the cell wall damage depending on the nature of the stress. Finally, 25 mutant strains showed enhanced caspofungin resistance, including 13 that had not been previously identified. Only three of them, wsc1δ, elo2δ and elo3δ, showed a significant decrease in β-1,3-glucan synthase activity. [Conclusions]: This work provides a global perspective about the mechanisms involved in cell wall stress adaptive responses and the cellular functions required for cell wall integrity. The results may be useful to uncover new potential antifungal targets and develop efficient antifungal strategies by combination of two drugs, one targeting the cell wall and the other interfering with the adaptive mechanisms.This work was supported by grants BIO2010-22146, BIO2013-48136-P (MINECO, Spain) and S2010/BMD-2414 (Comunidad de Madrid) to J.A, and grant BIO2012-35372 (MINECO, Spain) to JCR.Peer ReviewedBioMed CentralComunidad de MadridMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2017201720152017info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/156881reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#S2010/BMD-2414/PROMPTinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2013-48136-Phttps://doi.org/10.1186/s12864-015-1879-4Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1568812026-05-22T06:33:51Z
dc.title.none.fl_str_mv Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
title Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
spellingShingle Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
García, Raúl
Genomics
Chitin
β-1,3 glucan
Screening
Cell integrity
Fungal cell wall
title_short Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
title_full Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
title_fullStr Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
title_full_unstemmed Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
title_sort Genomic profiling of fungal cell wall-interfering compounds: identification of a common gene signature
dc.creator.none.fl_str_mv García, Raúl
Botet, Javier
Rodríguez-Peña, José Manuel
Bermejo, Clara
Ribas, Juan Carlos
Revuelta Doval, José Luis
Nombela, César
Arroyo, Javier
author García, Raúl
author_facet García, Raúl
Botet, Javier
Rodríguez-Peña, José Manuel
Bermejo, Clara
Ribas, Juan Carlos
Revuelta Doval, José Luis
Nombela, César
Arroyo, Javier
author_role author
author2 Botet, Javier
Rodríguez-Peña, José Manuel
Bermejo, Clara
Ribas, Juan Carlos
Revuelta Doval, José Luis
Nombela, César
Arroyo, Javier
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Genomics
Chitin
β-1,3 glucan
Screening
Cell integrity
Fungal cell wall
topic Genomics
Chitin
β-1,3 glucan
Screening
Cell integrity
Fungal cell wall
description [Background]: The fungal cell wall forms a compact network whose integrity is essential for cell morphology and viability. Thus, fungal cells have evolved mechanisms to elicit adequate adaptive responses when cell wall integrity (CWI) is compromised. Functional genomic approaches provide a unique opportunity to globally characterize these adaptive mechanisms. To provide a global perspective on these CWI regulatory mechanisms, we developed chemical-genomic profiling of haploid mutant budding yeast cells to systematically identify in parallel those genes required to cope with stresses interfering the cell wall by different modes of action: β-1,3 glucanase and chitinase activities (zymolyase), inhibition of β-1,3 glucan synthase (caspofungin) and binding to chitin (Congo red). [Results]: Measurement of the relative fitness of the whole collection of 4786 haploid budding yeast knock-out mutants identified 222 mutants hypersensitive to caspofungin, 154 mutants hypersensitive to zymolyase, and 446 mutants hypersensitive to Congo red. Functional profiling uncovered both common and specific requirements to cope with different cell wall damages. We identified a cluster of 43 genes highly important for the integrity of the cell wall as the common >signature of cell wall maintenance (CWM)>. This cluster was enriched in genes related to vesicular trafficking and transport, cell wall remodeling and morphogenesis, transcription and chromatin remodeling, signal transduction and RNA metabolism. Although the CWI pathway is the main MAPK pathway regulating cell wall integrity, the collaboration with other signal transduction pathways like the HOG pathway and the invasive growth pathway is also required to cope with the cell wall damage depending on the nature of the stress. Finally, 25 mutant strains showed enhanced caspofungin resistance, including 13 that had not been previously identified. Only three of them, wsc1δ, elo2δ and elo3δ, showed a significant decrease in β-1,3-glucan synthase activity. [Conclusions]: This work provides a global perspective about the mechanisms involved in cell wall stress adaptive responses and the cellular functions required for cell wall integrity. The results may be useful to uncover new potential antifungal targets and develop efficient antifungal strategies by combination of two drugs, one targeting the cell wall and the other interfering with the adaptive mechanisms.
publishDate 2015
dc.date.none.fl_str_mv 2015
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/10261/156881
url http://hdl.handle.net/10261/156881
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#
S2010/BMD-2414/PROMPT
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2013-48136-P
https://doi.org/10.1186/s12864-015-1879-4
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406812000747520
score 15.811543

Similares en LA Referencia