Biochemical Analysis of CaurSOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen Candida auris

Abstract

Candida auris is an emerging multidrug-resistant fungal pathogen. With high mortality rates, there is an urgent need for new antifungals to combat C. auris. Possible antifungal targets include Cu-only superoxide dismutases (SODs), extracellular SODs that are unique to fungi and effectively combat the superoxide burst of host immunity. Cu-only SODs are essential for the virulence of diverse fungal pathogens; however, little is understood about these enzymes in C. auris . We show here that C. auris secretes an enzymatically active Cu-only SOD (CaurSOD4) when cells are starved for Fe, a condition mimicking host environments. Although predicted to attach to cell walls, CaurSOD4 is detected as a soluble extracellular enzyme and can act at a distance to remove superoxide. CaurSOD4 selectively binds Cu and not Zn, and Cu binding is labile compared to bimetallic Cu/Zn SODs. Moreover, CaurSOD4 is susceptible to inhibition by various metal-binding drugs that are without effect on mammalian Cu/Zn SODs. Our studies highlight CaurSOD4 as a potential antifungal target worthy of consideration.