The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development

Aspergillus fumigatus is a major cause of human disease. The survival of this fungus is dependent on the cell wall organization and function of its components. The cell wall integrity pathway (CWIP) is the primary signaling cascade that controls de novo synthesis of the cell wall in fungi. Abundant...

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Autores: Rocha, Marina Campos, Fabri, João Henrique Tadini Marilhano, Simões, Isabelle Taira, Silva Rocha, Rafael, Hagiwara, Daisuke, da Cunha, Anderson Ferreira, Goldman, Gustavo Henrique, Cánovas López, David, Malavazi, Iran
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2020
País:España
Recursos:Universidad de Sevilla (US)
Repositório:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/142790
Acesso em linha:https://hdl.handle.net/11441/142790
https://doi.org/10.1128/AEM.02347-19
Access Level:Acceso aberto
Palavra-chave:Asexual development
Aspergillus fumigatus
Cell wall integrity
MpkA
PkcA
RlmA
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spelling The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual DevelopmentRocha, Marina CamposFabri, João Henrique Tadini MarilhanoSimões, Isabelle TairaSilva Rocha, RafaelHagiwara, Daisukeda Cunha, Anderson FerreiraGoldman, Gustavo HenriqueCánovas López, DavidMalavazi, IranAsexual developmentAspergillus fumigatusCell wall integrityMpkAPkcARlmAAspergillus fumigatus is a major cause of human disease. The survival of this fungus is dependent on the cell wall organization and function of its components. The cell wall integrity pathway (CWIP) is the primary signaling cascade that controls de novo synthesis of the cell wall in fungi. Abundant conidiation is a hallmark in A. fumigatus, and uptake of conidia by a susceptible host is usually the initial event in infection. The formation of conidia is mediated by the development of fungus-specific specialized structures, conidiophores, which are accompanied by cell wall remodeling. The molecular regulation of these changes in cell wall composition required for the rise of conidiophore from the solid surface and to disperse the conidia into the air is currently unknown. Here, we investigated the role of CWIP in conidiation. We show that CWIP pkcAG579R, ΔmpkA, and ΔrlmA mutants displayed reduced conidiation during synchronized asexual differentiation. The transcription factor RlmA directly regulated the expression of regulators of conidiation, including flbB, flbC, brlA, abaA, and rasB, as well as genes involved in cell wall synthesis and remodeling, and this affected the chitin content in aerial hyphae. Phosphorylation of RlmA and MpkA was increased during asexual differentiation. We also observed that MpkA physically associated with the proteins FlbB, FlbC, BrlA, and RasB during this process, suggesting another level of cross talk between the CWIP and asexual development pathways. In summary, our results support the conclusion that one function of the CWIP is the regulation of asexual development in filamentous fungi. IMPORTANCE A remarkable feature of the human pathogen Aspergillus fumigatus is its ability to produce impressive amounts of infectious propagules known as conidia. These particles reach immunocompromised patients and may initiate a life-threatening mycosis. The conidiation process in Aspergillus is governed by a sequence of proteins that coordinate the development of conidiophores. This process requires the remodeling of the cell wall so that the conidiophores can rise and withstand the chains of conidia. The events regulating cell wall remodeling during conidiation are currently unknown. Here, we show that the cell wall integrity pathway (CWIP) components RlmA and MpkA directly contribute to the activation of the conidiation cascade by enabling transcription or phosphorylation of critical proteins involved in asexual development. This study points to an essential role for the CWIP during conidiation and provides further insights into the complex regulation of asexual development in filamentous fungi.Fundação de Amparo à Pesquisa do Estado de São Paulo 2015/17541-0, 2016/07870-9, 2017/19694-3Conselho Nacional de Desenvolvimento Científico e Tecnológico 462383/2014-8American Society for MicrobiologyGenéticaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico. Brasil2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/142790https://doi.org/10.1128/AEM.02347-19reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésApplied and Environmental Microbiology, 86 (7), 2347.2015/17541-02016/07870-92017/19694-3462383/2014-8https://dx.doi.org/10.1128/AEM.02347-19info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1427902026-06-17T12:51:07Z
dc.title.none.fl_str_mv The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
title The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
spellingShingle The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
Rocha, Marina Campos
Asexual development
Aspergillus fumigatus
Cell wall integrity
MpkA
PkcA
RlmA
title_short The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
title_full The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
title_fullStr The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
title_full_unstemmed The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
title_sort The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus Fumigatus Asexual Development
dc.creator.none.fl_str_mv Rocha, Marina Campos
Fabri, João Henrique Tadini Marilhano
Simões, Isabelle Taira
Silva Rocha, Rafael
Hagiwara, Daisuke
da Cunha, Anderson Ferreira
Goldman, Gustavo Henrique
Cánovas López, David
Malavazi, Iran
author Rocha, Marina Campos
author_facet Rocha, Marina Campos
Fabri, João Henrique Tadini Marilhano
Simões, Isabelle Taira
Silva Rocha, Rafael
Hagiwara, Daisuke
da Cunha, Anderson Ferreira
Goldman, Gustavo Henrique
Cánovas López, David
Malavazi, Iran
author_role author
author2 Fabri, João Henrique Tadini Marilhano
Simões, Isabelle Taira
Silva Rocha, Rafael
Hagiwara, Daisuke
da Cunha, Anderson Ferreira
Goldman, Gustavo Henrique
Cánovas López, David
Malavazi, Iran
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Genética
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico. Brasil
dc.subject.none.fl_str_mv Asexual development
Aspergillus fumigatus
Cell wall integrity
MpkA
PkcA
RlmA
topic Asexual development
Aspergillus fumigatus
Cell wall integrity
MpkA
PkcA
RlmA
description Aspergillus fumigatus is a major cause of human disease. The survival of this fungus is dependent on the cell wall organization and function of its components. The cell wall integrity pathway (CWIP) is the primary signaling cascade that controls de novo synthesis of the cell wall in fungi. Abundant conidiation is a hallmark in A. fumigatus, and uptake of conidia by a susceptible host is usually the initial event in infection. The formation of conidia is mediated by the development of fungus-specific specialized structures, conidiophores, which are accompanied by cell wall remodeling. The molecular regulation of these changes in cell wall composition required for the rise of conidiophore from the solid surface and to disperse the conidia into the air is currently unknown. Here, we investigated the role of CWIP in conidiation. We show that CWIP pkcAG579R, ΔmpkA, and ΔrlmA mutants displayed reduced conidiation during synchronized asexual differentiation. The transcription factor RlmA directly regulated the expression of regulators of conidiation, including flbB, flbC, brlA, abaA, and rasB, as well as genes involved in cell wall synthesis and remodeling, and this affected the chitin content in aerial hyphae. Phosphorylation of RlmA and MpkA was increased during asexual differentiation. We also observed that MpkA physically associated with the proteins FlbB, FlbC, BrlA, and RasB during this process, suggesting another level of cross talk between the CWIP and asexual development pathways. In summary, our results support the conclusion that one function of the CWIP is the regulation of asexual development in filamentous fungi. IMPORTANCE A remarkable feature of the human pathogen Aspergillus fumigatus is its ability to produce impressive amounts of infectious propagules known as conidia. These particles reach immunocompromised patients and may initiate a life-threatening mycosis. The conidiation process in Aspergillus is governed by a sequence of proteins that coordinate the development of conidiophores. This process requires the remodeling of the cell wall so that the conidiophores can rise and withstand the chains of conidia. The events regulating cell wall remodeling during conidiation are currently unknown. Here, we show that the cell wall integrity pathway (CWIP) components RlmA and MpkA directly contribute to the activation of the conidiation cascade by enabling transcription or phosphorylation of critical proteins involved in asexual development. This study points to an essential role for the CWIP during conidiation and provides further insights into the complex regulation of asexual development in filamentous fungi.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/142790
https://doi.org/10.1128/AEM.02347-19
url https://hdl.handle.net/11441/142790
https://doi.org/10.1128/AEM.02347-19
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Applied and Environmental Microbiology, 86 (7), 2347.
2015/17541-0
2016/07870-9
2017/19694-3
462383/2014-8
https://dx.doi.org/10.1128/AEM.02347-19
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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