TY - JOUR
T1 - Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence
AU - Bruder Nascimento, Ariane Cristina Mendes de Oliveira
AU - dos Reis, Thaila Fernanda
AU - de Castro, Patrícia Alves
AU - Hori, Juliana I.
AU - Bom, Vinícius Leite Pedro
AU - de Assis, Leandro José
AU - Ramalho, Leandra Naira Zambelli
AU - Rocha, Marina Campos
AU - Malavazi, Iran
AU - Brown, Neil Andrew
AU - Valiante, Vito
AU - Brakhage, Axel A.
AU - Hagiwara, Daisuke
AU - Goldman, Gustavo H.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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. We investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein (MAP) 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. A. fumigatus ΔsakA and ΔmpkC were virulent in mouse survival experiments. In contrast, the ΔmpkC ΔsakA double mutant showed highly attenuated virulence. 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 cell wall biosynthesis.
AB - 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. We investigated which stress responses were influenced by the MpkC and SakA mitogen-activated protein (MAP) 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. A. fumigatus ΔsakA and ΔmpkC were virulent in mouse survival experiments. In contrast, the ΔmpkC ΔsakA double mutant showed highly attenuated virulence. 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 cell wall biosynthesis.
UR - http://www.scopus.com/inward/record.url?scp=84961781994&partnerID=8YFLogxK
U2 - 10.1111/mmi.13354
DO - 10.1111/mmi.13354
M3 - Article
C2 - 26878695
AN - SCOPUS:84961781994
SN - 0950-382X
VL - 100
SP - 841
EP - 859
JO - Molecular Microbiology
JF - Molecular Microbiology
IS - 5
ER -