title: The Aspergillus fumigatus SchASCH9kinase modulates SakAHOG1MAP kinase activity and it is essential for virulence.
abstract: The serine-threonine kinase TOR, the Target of Rapamycin, is an important regulator of nutrient, energy and stress signaling in eukaryotes. Sch9, a Ser/Thr kinase of AGC family (the cAMP-dependent PKA, cGMP- dependent protein kinase G and phospholipid-dependent protein kinase C family), is a substrate of TOR. Here, we characterized the fungal opportunistic pathogen Aspergillus fumigatus Sch9 homologue (SchA). The schA null mutant was sensitive to rapamycin, high concentrations of calcium, hyperosmotic stress and SchA was involved in iron metabolism. The ΔschA null mutant showed increased phosphorylation of SakA, the A. fumigatus Hog1 homologue. The schA null mutant has increased and decreased trehalose and glycerol accumulation, respectively, suggesting SchA performs different roles for glycerol and trehalose accumulation during osmotic stress. The schA was transcriptionally regulated by osmotic stress and this response was dependent on SakA and MpkC. The double ΔschA ΔsakA and ΔschA ΔmpkC mutants were more sensitive to osmotic stress than the corresponding parental strains. Transcriptomics and proteomics identified direct and indirect targets of SchA post-exposure to hyperosmotic stress. Finally, ΔschA was avirulent in a low dose murine infection model. Our results suggest there is a complex network of interactions amongst the A. fumigatus TOR, SakA and SchA pathways.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Alves de Castro
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: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Dolan
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Adriana
authors.initials: A
authors.lastname: Oliveira Manfiolli
authors.affiliation: Plant Biology and Crop Science, Rothamsted Research, Harpenden, Herts, AL5 2JQ, UK.
authors.forename: Neil Andrew
authors.initials: NA
authors.lastname: Brown
authors.affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jones
authors.affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland.
authors.forename: Sean
authors.initials: S
authors.lastname: Doyle
authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, Campinas, São Paulo, CEP 13083-970, Brasil.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Riaño-Pachón
authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, Campinas, São Paulo, CEP 13083-970, Brasil.
authors.forename: Fábio Márcio
authors.initials: FM
authors.lastname: Squina
authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Caixa Postal 6192, Campinas, São Paulo, CEP 13083-970, Brasil.|Max Planck Partner Group at Brazilian Bioethanol Science and Technology Laboratory, Brazilian Center for Research in Energy and Materials, São Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Caldana
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Del Poeta
authors.affiliation: Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Rafael
authors.initials: R
authors.lastname: Silva-Rocha
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; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000201:enzymology* / Q000378:metabolism / Q000472:pathogenicity*; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009997:Osmotic Pressure / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013172:Spores, Fungal / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; D020123:Sirolimus