Biochemical Analysis of Caur SOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen Candida auris

• Published in: ACS infectious diseases 2022-03, Vol.8 (3), p.584-595
• Main Authors: Chandler, Courtney E, Hernandez, Francisco G, Totten, Marissa, Robinett, Natalie G, Schatzman, Sabrina S, Zhang, Sean X, Culotta, Valeria C
• Format: Article
• Language: English
• Subjects: Animals; Antifungal Agents - pharmacology; Candida auris - drug effects; Candida auris - enzymology; Candida auris - metabolism; Candida auris - pathogenicity; Copper - metabolism; Drug Resistance, Multiple, Fungal - drug effects; Drug Resistance, Multiple, Fungal - physiology; Mammals - metabolism; Superoxide Dismutase - metabolism; Virulence - physiology; Zinc - metabolism
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.1c00590

is an emerging multidrug-resistant fungal pathogen. With high mortality rates, there is an urgent need for new antifungals to combat . 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 We show here that secretes an enzymatically active Cu-only SOD ( SOD4) when cells are starved for Fe, a condition mimicking host environments. Although predicted to attach to cell walls, SOD4 is detected as a soluble extracellular enzyme and can act at a distance to remove superoxide. SOD4 selectively binds Cu and not Zn, and Cu binding is labile compared to bimetallic Cu/Zn SODs. Moreover, SOD4 is susceptible to inhibition by various metal-binding drugs that are without effect on mammalian Cu/Zn SODs. Our studies highlight SOD4 as a potential antifungal target worthy of consideration.