Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence

Nascimento ACMDO Bruder; Reis TF dos; Castro PA de; JI Hori; VLP Bom; Leandro Jose De Assis; LNZ Ramalho; MC Rocha; I Malavazi; NA Brown; V Valiante; AA Brakhage; D Hagiwara; GH Goldman

doi:10.1111/mmi.13354

Mitogen activated protein kinases SakA^HOG1 and MpkC collaborate for Aspergillus fumigatus virulence

Nascimento ACMDO Bruder, Reis TF dos, Castro PA de, JI Hori, VLP Bom, Leandro Jose De Assis, LNZ Ramalho, MC Rocha, I Malavazi, NA Brown, V Valiante, AA Brakhage, D Hagiwara, GH Goldman

Peninsula Medical School

Research output: Contribution to journal › Article › peer-review

Abstract

SummaryHere, 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.

Original language	English
Pages (from-to)	841-859
Journal	Molecular Microbiology
Volume	100
Issue number	5
Early online date	23 Mar 2016
DOIs	https://doi.org/10.1111/mmi.13354
Publication status	Published - Jun 2016

Access to Document

10.1111/mmi.13354

Cite this

Bruder, N. ACMDO., dos, R. TF., de, C. PA., Hori, JI., Bom, VLP., De Assis, L. J., Ramalho, LNZ., Rocha, MC., Malavazi, I., Brown, NA., Valiante, V., Brakhage, AA., Hagiwara, D., & Goldman, GH. (2016). Mitogen activated protein kinases SakA^HOG1 and MpkC collaborate for Aspergillus fumigatus virulence. Molecular Microbiology, 100(5), 841-859. https://doi.org/10.1111/mmi.13354

@article{bf2b46c6e4074d54b74c176071489e07,

title = "Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence",

abstract = "SummaryHere, 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.",

author = "Bruder, {Nascimento ACMDO} and dos, {Reis TF} and de, {Castro PA} and JI Hori and VLP Bom and {De Assis}, {Leandro Jose} and LNZ Ramalho and MC Rocha and I Malavazi and NA Brown and V Valiante and AA Brakhage and D Hagiwara and GH Goldman",

year = "2016",

month = jun,

doi = "10.1111/mmi.13354",

language = "English",

volume = "100",

pages = "841--859",

journal = "Molecular Microbiology",

issn = "0950-382X",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "5",

}

TY - JOUR

T1 - Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence

AU - Bruder, Nascimento ACMDO

AU - dos, Reis TF

AU - de, Castro PA

AU - Hori, JI

AU - Bom, VLP

AU - De Assis, Leandro Jose

AU - Ramalho, LNZ

AU - Rocha, MC

AU - Malavazi, I

AU - Brown, NA

AU - Valiante, V

AU - Brakhage, AA

AU - Hagiwara, D

AU - Goldman, GH

PY - 2016/6

Y1 - 2016/6

N2 - SummaryHere, 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.

AB - SummaryHere, 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.

U2 - 10.1111/mmi.13354

DO - 10.1111/mmi.13354

M3 - Article

SN - 0950-382X

VL - 100

SP - 841

EP - 859

JO - Molecular Microbiology

JF - Molecular Microbiology

IS - 5

ER -

Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence

Abstract

Access to Document

Fingerprint

Cite this

Mitogen activated protein kinases SakA^HOG1 and MpkC collaborate for Aspergillus fumigatus virulence