RRC ID 46768
Author Bruder Nascimento AC, Dos Reis TF, de Castro PA, Hori JI, Bom VL, de Assis LJ, Ramalho LN, Rocha MC, Malavazi I, Brown NA, Valiante V, Brakhage AA, Hagiwara D, Goldman GH.
Title Mitogen activated protein kinases SakA(HOG1) and MpkC collaborate for Aspergillus fumigatus virulence.
Journal Mol Microbiol
Abstract Here, we investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein kinases of the high-osmolarity glycerol (HOG) pathway in the fungal pathogen Aspergillus fumigatus. The ΔsakA and the double ΔmpkC ΔsakA mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. Both MpkC::GFP and SakA::GFP translocated to the nucleus upon osmotic stress and cell wall damage, with SakA::GFP showing a quicker response. The phosphorylation state of MpkA was determined post exposure to high concentrations of congo red and Sorbitol. In the wild-type strain, MpkA phosphorylation levels progressively increased in both treatments. In contrast, the ΔsakA mutant had reduced MpkA phosphorylation, and surprisingly, the double ΔmpkC ΔsakA had no detectable MpkA phosphorylation. A. fumigatus ΔsakA and ΔmpkC were virulent in mouse survival experiments, but they had a 40% reduction in fungal burden. In contrast, the ΔmpkC ΔsakA double mutant showed highly attenuated virulence, with approximately 50% mice surviving and a 75% reduction in fungal burden. We propose that both cell wall integrity (CWI) and HOG pathways collaborate, and that MpkC could act by modulating SakA activity upon exposure to several types of stresses and during CW biosynthesis.
Volume 100(5)
Pages 841-59
Published 2016-6-1
DOI 10.1111/mmi.13354
PMID 26878695
MeSH Animals Aspergillus fumigatus / drug effects Aspergillus fumigatus / enzymology* Aspergillus fumigatus / genetics Aspergillus fumigatus / pathogenicity* Biofilms / growth & development Cell Wall / metabolism* Cell Wall / pathology Congo Red / pharmacology Fungal Proteins / genetics Fungal Proteins / metabolism* Gene Expression Regulation, Fungal Mice Mitogen-Activated Protein Kinases / genetics Mitogen-Activated Protein Kinases / metabolism* Mutation Osmotic Pressure Oxidative Stress Phosphorylation Signal Transduction Sorbitol / pharmacology Stress, Physiological Virulence
IF 3.418
Times Cited 34
Resource
Pathogenic microorganisms