Role of actin depolymerizing factor cofilin in Aspergillus fumigatus oxidative stress response and pathogenesis

Area of Science:

• Medical Mycology
• Molecular Biology
• Fungal Pathogenesis

Background:

• Aspergillus fumigatus causes most human aspergillosis cases.
• Cofilin is vital for cellular functions but its role in A. fumigatus is unexplored.

Purpose of the Study:

• To investigate the function of cofilin in Aspergillus fumigatus.
• To characterize the effects of cofilin overexpression on fungal physiology and virulence.

Main Methods:

• Construction of an A. fumigatus strain overexpressing cofilin (cofilin OE).
• Phenotypic analysis, including growth, stress resistance, and host cell interaction.
• Gene expression analysis of oxidative stress and cell wall synthesis pathways.
• Virulence assessment in murine and Galleria mellonella infection models.

Main Results:

• Cofilin OE strain showed increased resistance to H₂O₂ and diamide, and enhanced activation of the high osmolarity glycerol pathway.
• The cofilin OE strain exhibited increased internalization into lung epithelial cells and elevated inflammatory factor transcription (MCP-1, TNF-α, IL-8).
• Polysaccharide content (β-1, 3-glucan, chitin) and transcription of related genes increased in the cofilin OE strain.

Conclusions:

• Cofilin plays a significant role in regulating oxidative stress responses and cell wall polysaccharide synthesis in A. fumigatus.
• Despite altered physiological traits, cofilin overexpression did not affect the overall virulence of A. fumigatus in established infection models.