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RttA, a Zn2-Cys6 transcription factor in Aspergillus fumigatus, contributes to azole resistance

Summary

Researchers discovered that a protein called RttA helps a common fungus called Aspergillus fumigatus resist azole medicines, which are used to treat serious fungal infections. By studying how this protein works and which genes it controls, scientists found that RttA could be a new target for developing better antifungal treatments. The findings are important because azole-resistant fungal infections are becoming more common worldwide and harder to treat.

Background

Aspergillus fumigatus is the leading cause of aspergillosis, an opportunistic infection with high mortality rates despite antifungal treatment. Azole antifungals like voriconazole are primary treatments, but resistance is increasing due to environmental exposure to agricultural fungicides and clinical use.

Objective

To understand the role of RttA protein in azole resistance by conducting RNA-Seq analysis and functional studies using RttA deletion and overexpression strains in A. fumigatus.

Results

RttA was identified as a Zn2-Cys6 transcription factor with previously overlooked exons and domains. Deletion of rttA increased azole susceptibility while overexpression enhanced resistance. Six genes including ggtA and facC were identified as RttA-regulated targets with putative UPC2-binding motifs in their promoter regions.

Conclusion

RttA functions as a Zn2-Cys6 transcription factor that contributes to azole resistance by regulating multiple genes. Understanding RttA’s role provides insights into resistance mechanisms and highlights its potential as a therapeutic target for combating azole-resistant A. fumigatus.
  • Published in:Microbiology Spectrum,
  • Study Type:Experimental Study,
  • Source: 10.1128/spectrum.01810-25; PMID: 40839779
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