The Aspergillus fumigatus Phosphoproteome Reveals Roles of High-Osmolarity Glycerol Mitogen-Activated Protein Kinases in Promoting Cell Wall Damage and Caspofungin Tolerance

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dc.contributor.authorMattos, Eliciane Cevolani
dc.contributor.authorSilva, Lilian Pereira
dc.contributor.authorValero, Clara
dc.contributor.authorCastro, Patrícia Alves de
dc.contributor.authorReis, Thaila Fernanda dos
dc.contributor.authorRibeiro, Liliane F. C.
dc.contributor.authorMarten, Mark R.
dc.contributor.authorSilva-Rocha, Rafael
dc.contributor.authorWestmann, Cauã
dc.contributor.authorSilva, Carlos Henrique Tomich de Paula da
dc.contributor.authorTaft, Carlton Anthony
dc.contributor.authorAl-Furaiji, Narjes
dc.contributor.authorBromley, Michael
dc.contributor.authorMortensen, Uffe H.
dc.contributor.authorBenz, J. Philipp
dc.contributor.authorBrown, Neil Andrew
dc.contributor.authorGoldman, Gustavo H.
dc.date.accessioned2020-08-19T17:24:08Z
dc.date.available2020-08-19T17:24:08Z
dc.date.issued2020-02-04
dc.description.abstractThe filamentous fungus Aspergillus fumigatus can cause a distinct set of clinical disorders in humans. Invasive aspergillosis (IA) is the most common life-threatening fungal disease of immunocompromised humans. The mitogen-activated protein kinase (MAPK) signaling pathways are essential to the adaptation to the human host. Fungal cell survival is highly dependent on the organization, composition, and function of the cell wall. Here, an evaluation of the global A. fumigatus phosphoproteome under cell wall stress caused by the cell wall-damaging agent Congo red (CR) revealed 485 proteins potentially involved in the cell wall damage response. Comparative phosphoproteome analyses with the ΔsakA, ΔmpkC, and ΔsakA ΔmpkC mutant strains from the osmotic stress MAPK cascades identify their additional roles during the cell wall stress response. Our phosphoproteomics allowed the identification of novel kinases and transcription factors (TFs) involved in osmotic stress and in the cell wall integrity (CWI) pathway. Our global phosphoproteome network analysis showed an enrichment for protein kinases, RNA recognition motif domains, and the MAPK signaling pathway. In contrast to the wild-type strain, there is an overall decrease of differentially phosphorylated kinases and phosphatases in ΔsakA, ΔmpkC, and ΔsakA ΔmpkC mutants. We constructed phosphomutants for the phosphorylation sites of several proteins differentially phosphorylated in the wild-type and mutant strains. For all the phosphomutants, there is an increase in the sensitivity to cell wall-damaging agents and a reduction in the MpkA phosphorylation upon CR stress, suggesting these phosphosites could be important for the MpkA modulation and CWI pathway regulation.en_US
dc.description.sponsorshipWe thank Marcela Savoldi from FCFRP-USP for assisting us in some of the strain constructions. G.H.G. and E.C.M. conceived the study, and each designed and supervised substantial parts of it. E.C.M., L.P.S., C.V., P.A.C., T.F.D.R., L.F.C.R., R.S.-R., C.W., C.H.T.D.P.D.S., and C.A.T. performed the experiments and acquired the data. M.B. and N.A.F. provided some of the A. fumigatus deletion strains. All authors helped to analyze and interpret the data and read and approved the final manuscript. G.H.G. and E.C.M. drafted the manuscript, which was critically revised by M.R.M., M.B., U.H.M., J.P.B., and N.A.B. This study was funded by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grant number 2016/07870-9 and postdoctoral fellowship 2017/19288-5 and BEPE-FAPESP postdoctoral fellowship 2018/18043-1, the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and the Technical University of Munich-Institute for Advanced Study (TUMIAS), funded by the German Excellence Initiative awarded to G.H.G.en_US
dc.description.urihttps://mbio.asm.org/content/11/1/e02962-19en_US
dc.format.extent23 pagesen_US
dc.genrejournal articlesen_US
dc.identifierdoi:10.13016/m22gac-lkfq
dc.identifier.citationEliciane Cevolani Mattos et al., The Aspergillus fumigatus Phosphoproteome Reveals Roles of High-Osmolarity Glycerol Mitogen-Activated Protein Kinases in Promoting Cell Wall Damage and Caspofungin Tolerance, mBio Volume 11 Issue 1, DOI: 10.1128/mBio.02962-19en_US
dc.identifier.urihttps://doi.org/10.1128/mbio.02962-19
dc.identifier.urihttp://hdl.handle.net/11603/19460
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemical, Biochemical & Environmental Engineering Department Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.titleThe Aspergillus fumigatus Phosphoproteome Reveals Roles of High-Osmolarity Glycerol Mitogen-Activated Protein Kinases in Promoting Cell Wall Damage and Caspofungin Toleranceen_US
dc.typeTexten_US

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