Extracellular fungal Hsp90 represents a promising therapeutic target for combating fungal infections

Abstract

Heat shock protein 90 (Hsp90) is a pivotal virulence factor in pathogenic fungi, playing a significant role in conferring drug resistance. However, due to the high amino acid sequence similarity between fungal and mammalian Hsp90, targeting fungal intracellular Hsp90 therapeutically is associated with marked toxic side effects, thereby limiting clinical application. Studies have demonstrated that intracellular fungal Hsp90 can be secreted as extracellular Hsp90 (eHsp90), which plays a crucial role in fungal infections. Strategies targeting fungal eHsp90 have exhibited promising therapeutic outcomes. Unlike intracellular targeting, such antifungal approaches can operate without cell penetration, thereby circumventing the toxic side effects due to Hsp90′s high conservation. This review summarizes the potential extracellular secretion pathways of fungal eHsp90, its roles in fungal pathogenesis, as well as the development of vaccines and antibodies targeting fungal eHsp90. The review underlines the significance of eHsp90 in fungal infections and suggests that eHsp90 represents a promising therapeutic target for fungal infection treatment.