MYCOLab Ai Logo - gold and army green

The Gcn5 lysine acetyltransferase mediates cell wall remodeling, antifungal drug resistance, and virulence of Candida auris

Summary

Candida auris is a dangerous fungal infection that resists many standard antifungal drugs. Researchers discovered that a protein called Gcn5 helps this fungus survive both drugs and the body’s immune system. By targeting Gcn5 with a new compound called CPTH2, scientists showed they could make the fungus more vulnerable to standard treatments like caspofungin, suggesting a promising new approach to fighting these infections.

Background

Candida auris is a multidrug-resistant fungal pathogen causing infections with high morbidity and mortality. The molecular mechanisms underlying its drug resistance and host-pathogen interactions remain poorly understood. Previous studies showed that Gcn5 lysine acetyltransferase is important for antifungal resistance and virulence in Candida albicans.

Objective

To determine whether C. auris Gcn5 is essential for cell wall remodeling, antifungal drug resistance, and virulence. To identify Gcn5-dependent evolutionary conserved and divergent transcriptional networks between C. auris and C. albicans through comparative analysis.

Results

Gene set enrichment analysis revealed sphingolipid metabolism and GPI anchor biosynthesis pathways enriched in both species. C. auris gcn5Δ mutant showed increased β-glucan and chitin content. Gcn5 deficiency enhanced caspofungin susceptibility and reduced survival against phagocytes. KAT inhibitor CPTH2 showed potent antifungal activity alone and synergistically with caspofungin.

Conclusion

C. auris Gcn5 lysine acetyltransferase is essential for cell wall architecture, antifungal drug resistance, and virulence. Gcn5 represents a promising target for antifungal therapy, with potential for broad-spectrum applications.
  • Published in:mSphere,
  • Study Type:Experimental Study,
  • Source: PMID: 40066990, DOI: 10.1128/msphere.00069-25
Scroll to Top