Silva, Lilian Pereira and Frawley, Dean and de Assis, Leandro José and Tierney, Ciara and Fleming, Alastair B. and Bayram, Ozgur and Goldman, Gustavo H. (2020) Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon Sources. Msphere, 5 (5). e00818-20. ISSN 2379-5042

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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.

Item Type:	Article
Additional Information:	© 2020 Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by-sa/4.0/ Cite as: Putative Membrane Receptors Contribute to Activation and Efficient Signaling of Mitogen-Activated Protein Kinase Cascades during Adaptation of Aspergillus fumigatus to Different Stressors and Carbon Sources Lilian Pereira Silva, Dean Frawley, Leandro José de Assis, Ciara Tierney, Alastair B. Fleming, Ozgur Bayram, Gustavo Henrique Goldman mSphere Sep 2020, 5 (5) e00818-20; DOI: 10.1128/mSphere.00818-20
Keywords:	Aspergillus fumigatus; putative receptors; osmotic and cell wall stresses; high-osmolarity glycerol (HOG); caspofungin;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	13527
Identification Number:	https://doi.org/10.1128/mSphere.00818-20
Depositing User:	Ozgur Bayram
Date Deposited:	04 Nov 2020 17:28
Journal or Publication Title:	Msphere
Publisher:	American Society for Microbiology
Refereed:	Yes
Funders:	São Paulo Research Foundation (FAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Irish Research Council (IRC), Science Foundation Ireland (SFI)
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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