Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources

ABSTRACT The high-osmolarity glycerol (HOG) response pathway is a multifunctional signal transduction pathway that specifically transmits ambient osmotic signals. Saccharomyces cerevisiae Hog1p has two upstream signaling branches, the sensor histidine kinase Sln1p and the receptor Sho1p. The Sho1p b...

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Autores principales:	Lilian Pereira Silva, Dean Frawley, Leandro José de Assis, Ciara Tierney, Alastair B. Fleming, Ozgur Bayram, Gustavo Henrique Goldman
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Aspergillus fumigatus putative receptors osmotic and cell wall stresses high-osmolarity glycerol (HOG) caspofungin Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6b56b88db1ca4c4ab3654382f42d62bb
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spelling	oai:doaj.org-article:6b56b88db1ca4c4ab3654382f42d62bb2021-11-15T15:30:58ZPutative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources10.1128/mSphere.00818-202379-5042https://doaj.org/article/6b56b88db1ca4c4ab3654382f42d62bb2020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00818-20https://doaj.org/toc/2379-5042ABSTRACT The high-osmolarity glycerol (HOG) response pathway is a multifunctional signal transduction pathway that specifically transmits ambient osmotic signals. Saccharomyces cerevisiae Hog1p has two upstream signaling branches, the sensor histidine kinase Sln1p and the receptor Sho1p. The Sho1p branch includes two other proteins, the Msb2p mucin and Opy2p. Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Here, we investigated the roles played by A. fumigatus SlnASln1p, ShoASho1p, MsbAMsb2p, and OpyAOpy2p putative homologues during the activation of the mitogen-activated protein kinase (MAPK) HOG pathway. The shoA, msbA, and opyA singly and doubly null mutants are important for the cell wall integrity (CWI) pathway, oxidative stress, and virulence as assessed by a Galleria mellonella model. Genetic interactions of ShoA, MsbA, and OpyA are also important for proper activation of the SakAHog1p and MpkASlt2 cascade and the response to osmotic and cell wall stresses. Comparative label-free quantitative proteomics analysis of the singly null mutants with the wild-type strain upon caspofungin exposure indicates that the absence of ShoA, MsbA, and OpyA affects the osmotic stress response, carbohydrate metabolism, and protein degradation. The putative receptor mutants showed altered trehalose and glycogen accumulation, suggesting a role for ShoA, MsbA, and OpyA in sugar storage. Protein kinase A activity was also decreased in these mutants. We also observed genetic interactions between SlnA, ShoA, MsbA, and OpyA, suggesting that both branches are important for activation of the HOG/CWI pathways. Our results help in the understanding of the activation and modulation of the HOG and CWI pathways in this important fungal pathogen. IMPORTANCE Aspergillus fumigatus is an important human-pathogenic fungal species that is responsible for a high incidence of infections in immunocompromised individuals. A. fumigatus high-osmolarity glycerol (HOG) and cell wall integrity pathways are important for the adaptation to different forms of environmental adversity such as osmotic and oxidative stresses, nutrient limitations, high temperatures, and other chemical and mechanical stresses that may be produced by the host immune system and antifungal drugs. Little is known about how these pathways are activated in this fungal pathogen. Here, we characterize four A. fumigatus putative homologues that are important for the activation of the yeast HOG pathway. A. fumigatus SlnASln1p, ShoASho1p, MsbAMsb2p, and OpyAOpy2p are genetically interacting and are essential for the activation of the HOG and cell wall integrity pathways. Our results contribute to the understanding of A. fumigatus adaptation to the host environment.Lilian Pereira SilvaDean FrawleyLeandro José de AssisCiara TierneyAlastair B. FlemingOzgur BayramGustavo Henrique GoldmanAmerican Society for MicrobiologyarticleAspergillus fumigatusputative receptorsosmotic and cell wall stresseshigh-osmolarity glycerol (HOG)caspofunginMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus putative receptors osmotic and cell wall stresses high-osmolarity glycerol (HOG) caspofungin Microbiology QR1-502
spellingShingle	Aspergillus fumigatus putative receptors osmotic and cell wall stresses high-osmolarity glycerol (HOG) caspofungin Microbiology QR1-502 Lilian Pereira Silva Dean Frawley Leandro José de Assis Ciara Tierney Alastair B. Fleming Ozgur Bayram Gustavo Henrique Goldman Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources
description	ABSTRACT The high-osmolarity glycerol (HOG) response pathway is a multifunctional signal transduction pathway that specifically transmits ambient osmotic signals. Saccharomyces cerevisiae Hog1p has two upstream signaling branches, the sensor histidine kinase Sln1p and the receptor Sho1p. The Sho1p branch includes two other proteins, the Msb2p mucin and Opy2p. Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Here, we investigated the roles played by A. fumigatus SlnASln1p, ShoASho1p, MsbAMsb2p, and OpyAOpy2p putative homologues during the activation of the mitogen-activated protein kinase (MAPK) HOG pathway. The shoA, msbA, and opyA singly and doubly null mutants are important for the cell wall integrity (CWI) pathway, oxidative stress, and virulence as assessed by a Galleria mellonella model. Genetic interactions of ShoA, MsbA, and OpyA are also important for proper activation of the SakAHog1p and MpkASlt2 cascade and the response to osmotic and cell wall stresses. Comparative label-free quantitative proteomics analysis of the singly null mutants with the wild-type strain upon caspofungin exposure indicates that the absence of ShoA, MsbA, and OpyA affects the osmotic stress response, carbohydrate metabolism, and protein degradation. The putative receptor mutants showed altered trehalose and glycogen accumulation, suggesting a role for ShoA, MsbA, and OpyA in sugar storage. Protein kinase A activity was also decreased in these mutants. We also observed genetic interactions between SlnA, ShoA, MsbA, and OpyA, suggesting that both branches are important for activation of the HOG/CWI pathways. Our results help in the understanding of the activation and modulation of the HOG and CWI pathways in this important fungal pathogen. IMPORTANCE Aspergillus fumigatus is an important human-pathogenic fungal species that is responsible for a high incidence of infections in immunocompromised individuals. A. fumigatus high-osmolarity glycerol (HOG) and cell wall integrity pathways are important for the adaptation to different forms of environmental adversity such as osmotic and oxidative stresses, nutrient limitations, high temperatures, and other chemical and mechanical stresses that may be produced by the host immune system and antifungal drugs. Little is known about how these pathways are activated in this fungal pathogen. Here, we characterize four A. fumigatus putative homologues that are important for the activation of the yeast HOG pathway. A. fumigatus SlnASln1p, ShoASho1p, MsbAMsb2p, and OpyAOpy2p are genetically interacting and are essential for the activation of the HOG and cell wall integrity pathways. Our results contribute to the understanding of A. fumigatus adaptation to the host environment.
format	article
author	Lilian Pereira Silva Dean Frawley Leandro José de Assis Ciara Tierney Alastair B. Fleming Ozgur Bayram Gustavo Henrique Goldman
author_facet	Lilian Pereira Silva Dean Frawley Leandro José de Assis Ciara Tierney Alastair B. Fleming Ozgur Bayram Gustavo Henrique Goldman
author_sort	Lilian Pereira Silva
title	Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources
title_short	Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources
title_full	Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources
title_fullStr	Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources
title_full_unstemmed	Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources
title_sort	putative membrane receptors contribute to activation and efficient signaling of mitogen-activated protein kinase cascades during adaptation of <named-content content-type="genus-species">aspergillus fumigatus</named-content> to different stressors and carbon sources
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/6b56b88db1ca4c4ab3654382f42d62bb
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Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of <named-content content-type="genus-species">Aspergillus fumigatus</named-content> to Different Stressors and Carbon Sources

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