Mitogen activated protein kinases SakAHOG1 and MpkC collaborate for Aspergillus fumigatus virulence. Issue 5 (23rd March 2016)

• Record Type: Journal Article
• Authors: Bruder Nascimento, Ariane Cristina Mendes de Oliveira; dos Reis, Thaila Fernanda; de Castro, Patrícia Alves; Hori, Juliana I.; Bom, Vinícius Leite Pedro; de Assis, Leandro José; Ramalho, Leandra Naira Zambelli; Rocha, Marina Campos; Malavazi, Iran; Brown, Neil Andrew; Valiante, Vito; Brakhage, Axel A.; Hagiwara, Daisuke; Goldman, Gustavo H.
• Is Part Of: Molecular microbiology. Volume 100:Issue 5(2016)
• Page Start: 841
• Page End: 859
• Publication Date: 2016-03-23
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13354
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: 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 Δ sakA and the double Δ mpkC Δ sakA 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 Δ sakA mutant had reduced MpkA phosphorylation, and surprisingly, the double Δ mpkC Δ sakA had no detectable MpkA phosphorylation. A. fumigatus Δ sakA and Δ mpkC were virulent in mouse survival experiments, but they had a 40% reduction in fungal burden. In contrast, the Δ mpkC Δ sakA 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. Abstract : 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 Δ sakA and the double Δ mpkC Δ sakA mutants were more sensitive to osmotic and oxidative stresses, and to cell wall damaging agents. A. fumigatus Δ sakA and Δ mpkC were virulent in mouse survival experiments. In contrast, the Δ mpkC Δ sakA 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.