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    Aspergillus fumigatus High Osmolarity Glycerol Mitogen Activated Protein Kinases SakA and MpkC Physically Interact During Osmotic and Cell Wall Stresses


    Manfiolli, Adriana Oliveira and Mattos, Eliciane Cevolani and de Assis, Leandro José and Silva, Lilian Pereira and Ulas, Mevlut and Brown, Neil Andrew and Bayram, Ozgur and Goldman, Gustavo H. (2019) Aspergillus fumigatus High Osmolarity Glycerol Mitogen Activated Protein Kinases SakA and MpkC Physically Interact During Osmotic and Cell Wall Stresses. Frontiers in Microbiology, 10 (918). ISSN 1664-302X

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    Abstract

    Aspergillus fumigatus, a saprophytic filamentous fungus, is a serious opportunistic pathogen of mammals and it is the primary causal agent of invasive aspergillosis (IA). Mitogen activated protein Kinases (MAPKs) are important components involved in diverse cellular processes in eukaryotes. A. fumigatus MpkC and SakA, the homologs of the Saccharomyces cerevisiae Hog1 are important to adaptations to oxidative and osmotic stresses, heat shock, cell wall damage, macrophage recognition, and full virulence. We performed protein pull-down experiments aiming to identify interaction partners of SakA and MpkC by mass spectrometry analysis. In presence of osmotic stress with sorbitol, 118, and 213 proteins were detected as possible protein interactors of SakA and MpkC, respectively. Under cell wall stress caused by congo red, 420 and 299 proteins were detected interacting with SakA and MpkC, respectively. Interestingly, a group of 78 and 256 proteins were common to both interactome analysis. Co-immunoprecipitation (Co-IP) experiments showed that SakA::GFP is physically associated with MpkC:3xHA upon osmotic and cell wall stresses. We also validated the association between SakA:GFP and the cell wall integrity MAPK MpkA:3xHA and the phosphatase PtcB:3xHA, under cell wall stress. We further characterized A. fumigatus PakA, the homolog of the S. cerevisiae sexual developmental serine/threonine kinase Ste20, as a component of the SakA/MpkC MAPK pathway. The ΔpakA strain is more sensitive to cell wall damaging agents as congo red, calcofluor white, and caspofungin. Together, our data supporting the hypothesis that SakA and MpkC are part of an osmotic and general signal pathways involved in regulation of the response to the cell wall damage, oxidative stress, drug resistance, and establishment of infection. This manuscript describes an important biological resource to understand SakA and MpkC protein interactions. Further investigation of the biological roles played by these protein interactors will provide more opportunities to understand and combat IA.

    Item Type: Article
    Additional Information: Copyright © 2019 Manfiolli, Mattos, de Assis, Silva, Ula¸s, Brown, Silva-Rocha, Bayram and Goldman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Citation: Manfiolli AO, Mattos EC, de Assis LJ, Silva LP, Ulas¸ M, Brown NA, Silva-Rocha R, Bayram Ö and Goldman GH (2019) Aspergillus fumigatus High Osmolarity Glycerol Mitogen Activated Protein Kinases SakA and MpkC Physically Interact During Osmotic and Cell Wall Stresses. Front. Microbiol. 10:918. doi: 10.3389/fmicb.2019.00918
    Keywords: Aspergillus fumigatus; mitogen activate protein kinase; HOG; MPKC; SakA;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 10994
    Identification Number: https://doi.org/10.3389/fmicb.2019.00918
    Depositing User: Ozgur Bayram
    Date Deposited: 28 Aug 2019 13:59
    Journal or Publication Title: Frontiers in Microbiology
    Publisher: Frontiers
    Refereed: Yes
    URI:

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