The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence. Issue 4 (7th October 2016)

• Record Type: Journal Article
• Authors: Alves de Castro, Patrícia; dos Reis, Thaila Fernanda; Dolan, Stephen K.; Oliveira Manfiolli, Adriana; Brown, Neil Andrew; Jones, Gary W.; Doyle, Sean; Riaño‐Pachón, Diego M.; Squina, Fábio Márcio; Caldana, Camila; Singh, Ashutosh; Del Poeta, Maurizio; Hagiwara, Daisuke; Silva‐Rocha, Rafael; Goldman, Gustavo H.
• Is Part Of: Molecular microbiology. Volume 102:Issue 4(2016)
• Page Start: 642
• Page End: 671
• Publication Date: 2016-10-07
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13484
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: 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 Δ schA 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, Δ schA 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. Abstract : Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. We characterized the A. fumigatus Sch9 homologue (SchA) showing that SchA is important for integrating calcium signalling, sphingolipid biosynthesis, hyperosmotic stress, and was involved in iron metabolism. The ΔschA was avirulent in a low dose murine infection model. SchA represents an important protein kinase at the interface between osmotic stress, iron sensing, sphingolipid biosynthesis, calcium metabolism, and pathogenicity in this important opportunistic human pathogen.