title: Genome-wide transcriptome analysis of Aspergillus fumigatus exposed to osmotic stress reveals regulators of osmotic and cell wall stresses that are SakAHOG1and MpkC dependent.
abstract: Invasive aspergillosis is predominantly caused by Aspergillus fumigatus, and adaptations to stresses experienced within the human host are a prerequisite for the survival and virulence strategies of the pathogen. The central signal transduction pathway operating during hyperosmotic stress is the high osmolarity glycerol mitogen-activated protein kinase cascade. A. fumigatus MpkC and SakA, orthologues of the Saccharomyces cerevisiae Hog1p, constitute the primary regulator of the hyperosmotic stress response. We compared A. fumigatus wild-type transcriptional response to osmotic stress with the ΔmpkC, ΔsakA, and ΔmpkC ΔsakA strains. Our results strongly indicate that MpkC and SakA have independent and collaborative functions during the transcriptional response to transient osmotic stress. We have identified and characterized null mutants for four A. fumigatus basic leucine zipper proteins transcription factors. The atfA and atfB have comparable expression levels with the wild-type in ΔmpkC but are repressed in ΔsakA and ΔmpkC ΔsakA post-osmotic stress. The atfC and atfD have reduced expression levels in all mutants post-osmotic stress. The atfA-D null mutants displayed several phenotypes related to osmotic, oxidative, and cell wall stresses. The ΔatfA and ΔatfB were shown to be avirulent and to have attenuated virulence, respectively, in both Galleria mellonella and a neutropenic murine model of invasive pulmonary aspergillosis.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Lilian
authors.initials: L
authors.lastname: Pereira Silva
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: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Mario Henrique
authors.initials: MH
authors.lastname: Paziani
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil.
authors.forename: Márcia Regina
authors.initials: MR
authors.lastname: Von Zeska Kress
authors.affiliation: Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), São Paulo, Brazil.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Riaño-Pachón
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: Laure N A
authors.initials: LN
authors.lastname: Ries
authors.affiliation: Plant Biology and Crop Science, Rothamsted Research, Harpenden, Hertfordshire, UK.
authors.forename: Neil Andrew
authors.initials: NA
authors.lastname: Brown
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* / Q000235:genetics; D002473:Cell Wall; D005260:Female; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D063990:Gene Ontology; D016681:Genome, Fungal; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism; D009997:Osmotic Pressure; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000502:physiology; D059467:Transcriptome
chemical_list: D005656:Fungal Proteins; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases