RRC ID 52829
Author Alves de Castro P, Dos Reis TF, Dolan SK, Oliveira Manfiolli A, Brown NA, Jones GW, Doyle S, Riaño-Pachón DM, Squina FM, Caldana C, Singh A, Del Poeta M, Hagiwara D, Silva-Rocha R, Goldman GH.
Title The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence.
Journal Mol Microbiol
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.
Volume 102(4)
Pages 642-671
Published 2016-11-1
DOI 10.1111/mmi.13484
PMID 27538790
PMC PMC5207228
MeSH Animals Aspergillosis / microbiology Aspergillus fumigatus / enzymology* Aspergillus fumigatus / metabolism Aspergillus fumigatus / pathogenicity* Female Fungal Proteins / metabolism MAP Kinase Signaling System Mice Mice, Inbred BALB C Mitogen-Activated Protein Kinases / metabolism* Osmotic Pressure / physiology Oxidative Stress / genetics Oxidative Stress / physiology Phosphorylation Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism Signal Transduction Sirolimus / pharmacology Spores, Fungal / metabolism TOR Serine-Threonine Kinases / genetics TOR Serine-Threonine Kinases / metabolism Virulence
IF 3.418
Times Cited 8
Pathogenic microorganisms