The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence

Patrícia Alves de Castro, Thaila Fernanda dos Reis, Stephen K. Dolan, Adriana Oliveira Manfiolli, Neil Andrew Brown, Gary W. Jones, Sean Doyle, Diego M. Riaño-Pachón, Fábio Márcio Squina, Camila Caldana, Ashutosh Singh, Maurizio Del Poeta, Daisuke Hagiwara, Rafael Silva-Rocha, Gustavo H. Goldman

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)642-671
Number of pages30
JournalMolecular Microbiology
Volume102
Issue number4
DOIs
Publication statusPublished - 1 Nov 2016

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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