CDI: C. auris Gcn5: Drug Resistance, Virulence, and Therapy Target
- Ray Sullivan
- May 1
- 1 min read
The human infectious fungus Candida auris poses a significant global human health burden. C. auris is classified as an urgent threat by the CDC and a priority pathogen by the WHO due to its multidrug resistance, high transmissibility, and lack of effective treatments. New therapeutic approaches are needed. The Chauhan and Desai Labs at Hackensack Meridian Health Center for Discovery & Innovation demonstrated that the C. auris Gcn5 lysine acetyltransferase is essential for its survival, mediating both antifungal drug resistance (specifically to caspofungin) and virulence. Gcn5 impacts C. auris by regulating cell wall composition (increasing β-glucan and chitin exposure in the absence of Gcn5) and influencing immune cell interactions. Genetic deletion of GCN5 significantly attenuates C. auris virulence in a murine model. Gcn5 is a promising target for antifungal drug discovery due to its critical role in C. auris pathogenesis and the structural differences between fungal and mammalian Gcn5. Pharmacological inhibition of Gcn5 using cyclopentanone, 2-[4-(4-chlorophenyl)-2-thiazolyl] hydrazone (CPTH2) shows antifungal activity and synergistic effects with caspofungin against drug-resistant C. auris. Their findings strongly support the exploration of fungal Gcn5 as a novel and much-needed target for developing new antifungal drugs to combat the growing threat of C. auris infections.
Chauhan M, Shivarathri R, Aptekmann AA, Chowdhary A, Kuchler K, Desai JV, Chauhan N. The Gcn5 lysine acetyltransferase mediates cell wall remodeling, antifungal drug resistance, and virulence of Candida auris. mSphere. 2025 Apr 29;10(4):e0006925. doi: 10.1128/msphere.00069-25. Epub 2025 Mar 11. PMID: 40066990; PMCID: PMC12039264.
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