Suppression of Hsp90 expression in <i>Aspergillus fumigatus</i> enhances sensitivity to oxidative stress and activates host cell NF-κB p65 and ERK signaling pathways

The significance of this study lies in its focused and in-depth analysis of the critical roles of the molecular chaperone Hsp90 in oxidative stress tolerance, metal ion homeostasis, and immune response regulation in <i>Aspergillus fumigatus</i>. Utilizing the Tet-on system to precisely modulate Hsp90 expression, this research demonstrates that Hsp90 is essential for the growth, development, and pathogenicity of this major opportunistic pathogen. Specifically, the study highlights Hsp90's crucial role in sustaining antioxidant enzyme activity, maintaining metal ion balance, and regulating immune responses-key factors that enable the fungus to survive and infect the host. These findings provide novel insights into the molecular mechanisms that underlie <i>A. fumigatus</i>'s resistance to oxidative stress and its evasion of host immunity, positioning Hsp90 as a promising therapeutic target for treating fungal infections. Furthermore, the results open new avenues for future investigations into the role of Hsp90 in fungal pathogenesis and immune modulation, potentially guiding the development of targeted antifungal therapies.