title: Mitogen activated protein kinases SakA(HOG1) and MpkC collaborate for Aspergillus fumigatus virulence.
abstract: Here, we investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein kinases of the high-osmolarity glycerol (HOG) pathway in the fungal pathogen Aspergillus fumigatus. The ΔsakA and the double ΔmpkC ΔsakA mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. Both MpkC::GFP and SakA::GFP translocated to the nucleus upon osmotic stress and cell wall damage, with SakA::GFP showing a quicker response. The phosphorylation state of MpkA was determined post exposure to high concentrations of congo red and Sorbitol. In the wild-type strain, MpkA phosphorylation levels progressively increased in both treatments. In contrast, the ΔsakA mutant had reduced MpkA phosphorylation, and surprisingly, the double ΔmpkC ΔsakA had no detectable MpkA phosphorylation. A. fumigatus ΔsakA and ΔmpkC were virulent in mouse survival experiments, but they had a 40% reduction in fungal burden. In contrast, the ΔmpkC ΔsakA double mutant showed highly attenuated virulence, with approximately 50% mice surviving and a 75% reduction in fungal burden. We propose that both cell wall integrity (CWI) and HOG pathways collaborate, and that MpkC could act by modulating SakA activity upon exposure to several types of stresses and during CW biosynthesis.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Ariane Cristina Mendes de Oliveira
authors.initials: AC
authors.lastname: Bruder Nascimento
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Thaila Fernanda
authors.initials: TF
authors.lastname: Dos Reis
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Patrícia Alves
authors.initials: PA
authors.lastname: de Castro
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Juliana I
authors.initials: JI
authors.lastname: Hori
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Vinícius Leite Pedro
authors.initials: VL
authors.lastname: Bom
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Leandro José
authors.initials: LJ
authors.lastname: de Assis
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Leandra Naira Zambelli
authors.initials: LN
authors.lastname: Ramalho
authors.affiliation: Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Marina Campos
authors.initials: MC
authors.lastname: Rocha
authors.affiliation: Departamento de Genética e Evolução, Centro de Ciências Biológicas e da Saúde, Universidade Federal de São Carlos, São Carlos, São Paulo, Brazil.
authors.forename: Iran
authors.initials: I
authors.lastname: Malavazi
authors.affiliation: Plant Science and Crop Biology, Rothamsted Research, Harpenden, Hertfordshire, UK.
authors.forename: Neil Andrew
authors.initials: NA
authors.lastname: Brown
authors.affiliation: Leibniz Junior Research Group Biobricks of Microbial Natural Product Syntheses, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.
authors.forename: Vito
authors.initials: V
authors.lastname: Valiante
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology (HKI), Jena, Germany; Institute for Microbiology, Friedrich Schiller University, Jena, Germany.
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D018441:Biofilms / Q000254:growth & development; D002473:Cell Wall / Q000378:metabolism* / Q000473:pathology; D003224:Congo Red / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009997:Osmotic Pressure; D018384:Oxidative Stress; D010766:Phosphorylation; D015398:Signal Transduction; D013012:Sorbitol / Q000494:pharmacology; D013312:Stress, Physiological; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D003224:Congo Red; D013012:Sorbitol; D020928:Mitogen-Activated Protein Kinases