Genome-wide transcriptome analysis of Aspergillus fumigatus exposed to osmotic stress reveals regulators of osmotic and cell wall stresses that are SakAHOG1 and MpkC dependent

Lilian Pereira Silva, Patrícia Alves de Castro, Thaila Fernanda dos Reis, Mario Henrique Paziani, Márcia Regina Von Zeska Kress, Diego M. Riaño-Pachón, Daisuke Hagiwara, Laure N.A. Ries, Neil Andrew Brown, Gustavo H. Goldman

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47 Citations (SciVal)

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.

Original languageEnglish
Article numbere12681
JournalCellular Microbiology
Volume19
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017

Funding

We gratefully acknowledge the provision of time by the NGS facility at Laboratório Nacional de Ciência e Tecnologia do Bioetanol (CTBE) that integrates the Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). We thank Mr. Douglas Antonio Alvaredo Paixão for his help during the construction of the RNASeq libraries, as well as Dr Iran Malavazi and Marina Rocha for providing the RNAs for the caspofungin induction. We would like to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for providing financial support. Rothamsted Research receives grant-aided support from the Biotechnology and Biological Sciences Research Council (BBSRC) UK as part of the Institute Strategic Programme 20:20® wheat [BB/J/00426X/1]. Neil Brown was supported by the BBSRC Future Leader Fellowship [BB/N011686/1]. We also thank the two anonymous reviewers and the editor for their suggestions and comments.

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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