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

Area of Science:

• Mycology
• Molecular Biology
• Fungal Pathogenesis

Background:

• The high-osmolarity glycerol (HOG) pathway is crucial for fungal stress response.
• Mitogen-activated protein kinases (MAPKs) MpkC and SakA are key components of the HOG pathway in Aspergillus fumigatus.
• Understanding their roles is vital for combating fungal infections.

Purpose of the Study:

• To investigate the roles of MpkC and SakA in Aspergillus fumigatus stress responses.
• To elucidate the interplay between the HOG pathway and cell wall integrity (CWI) pathways.
• To assess the impact of these MAPKs on fungal virulence.

Main Methods:

• Generating and analyzing single (ΔsakA) and double (ΔmpkC ΔsakA) mutants.
• Assessing sensitivity to osmotic, oxidative, and cell wall damaging stresses.
• Utilizing fluorescently tagged proteins (MpkC::GFP, SakA::GFP) for subcellular localization studies.
• Measuring MpkA phosphorylation levels.
• Conducting mouse survival experiments to evaluate virulence and fungal burden.

Main Results:

• ΔsakA and ΔmpkC ΔsakA mutants exhibited increased sensitivity to various stresses.
• MpkC and SakA localized to the nucleus upon stress, with SakA responding faster.
• MpkA phosphorylation was dependent on SakA and MpkC.
• The ΔmpkC ΔsakA double mutant showed significantly reduced virulence and fungal burden in mice.

Conclusions:

• MpkC and SakA are essential for Aspergillus fumigatus stress tolerance and virulence.
• The HOG pathway, involving MpkC and SakA, collaborates with the CWI pathway.
• MpkC may regulate SakA activity during stress and cell wall biosynthesis.