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

A - Papers appearing in refereed journals

Alves de Castro, P., Dos Reis, Thaila F., Dolan, S. K., Oliveira Manfiolli, A., Brown, N. A., Jones, G. W., Doyle, S., Riano-Pachon, D. M., Squina, F. M., Caldana, C., Singh, A., Del Poeta, M., Hagiwara, D., Silva-Rocha, R. and Goldman, G. H. 2016. The Aspergillus fumigatus SchASCH9 kinase modulates SakAHOG1 MAP kinase activity and it is essential for virulence. Molecular Microbiology. 102 (4), pp. 642-671. https://doi.org/10.1111/mmi.13484

AuthorsAlves de Castro, P., Dos Reis, Thaila F., Dolan, S. K., Oliveira Manfiolli, A., Brown, N. A., Jones, G. W., Doyle, S., Riano-Pachon, D. M., Squina, F. M., Caldana, C., Singh, A., Del Poeta, M., Hagiwara, D., Silva-Rocha, R. and Goldman, G. H.
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 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 schA sakA and schA mpkC 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, 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.

KeywordsBiochemistry & Molecular Biology; Microbiology
Year of Publication2016
JournalMolecular Microbiology
Journal citation102 (4), pp. 642-671
Digital Object Identifier (DOI)https://doi.org/10.1111/mmi.13484
Open accessPublished as bronze (free) open access
FunderIrish Research Council Embark PhD Fellowship
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Science Foundation Ireland
Publisher's version
Output statusPublished
Publication dates
Online19 Aug 2016
ISSN0950382X
0950-382X
PublisherWiley
Copyright licensePublisher copyright
Grant IDSFI/12/ISCA/2494

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