Calcineurin as a multifunctional regulator: Unraveling novel functions in fungal stress responses, hyphal growth, drug resistance, and pathogenesis

• Calcineurin regulates stress responses and growth in yeasts and filamentous fungi.
• Calcineurin is important for virulence of several plant and human fungal pathogens.
• Calcineurin inhibitors are active in vitro against major invasive fungal pathogens.
• Immunosuppressive nature of calcineurin inhibitors limit their usage as antifungals.
• Understanding calcineurin roles in fungi might lead to designing novel antifungals.

Calcineurin signaling plays diverse roles in fungi in regulating stress responses, morphogenesis and pathogenesis. Although calcineurin signaling is conserved among fungi, recent studies indicate important divergences in calcineurin-dependent cellular functions among different human fungal pathogens. Fungal pathogens utilize the calcineurin pathway to effectively survive the host environment and cause life-threatening infections. The immunosuppressive calcineurin inhibitors (FK506 and cyclosporine A) are active against fungi, making targeting calcineurin a promising antifungal drug development strategy. Here we summarize current knowledge on calcineurin in yeasts and filamentous fungi, and review the importance of understanding fungal-specific attributes of calcineurin to decipher fungal pathogenesis and develop novel antifungal therapeutic approaches.