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Aspergillus fumigatus ctf1 – a novel zinc finger transcription factor involved in azole resistance

Summary

A. fumigatus is a dangerous fungal infection that kills many immunocompromised patients and increasingly resists common antifungal drugs. Researchers identified a key protein called ctf1 that helps the fungus resist the drug voriconazole by pumping it out of fungal cells and altering the fungal cell membrane. Understanding how ctf1 works could lead to new treatments for these difficult-to-treat infections.

Background

Aspergillus fumigatus is a major cause of opportunistic mold infections in immunocompromised populations with high morbidity and mortality rates. Antifungal resistance mechanisms in A. fumigatus are not fully understood, limiting treatment effectiveness. This study investigates the function of ctf1, a gene encoding a C6 transcription factor with homology to Mrr2.

Objective

To elucidate the function of ctf1 (AFUA_1G03800) in A. fumigatus and its role in azole resistance. The study aimed to determine how ctf1 affects fungal growth, morphology, and susceptibility to triazole antifungals.

Results

ctf1 deletion resulted in slower growth and reduced conidia production. The knockout strain showed 2-fold decreased susceptibility to voriconazole. Increased ergosterol content and overexpression of mdr1, mdr2, and mdr4 efflux pump genes were observed in the knockout strain, while cyp51A and cyp51B expression remained unchanged.

Conclusion

ctf1 is a novel C6 transcription factor that regulates A. fumigatus growth, metabolism, and antifungal resistance primarily through efflux pump-mediated mechanisms and ergosterol biosynthesis. Understanding ctf1 function contributes to elucidating A. fumigatus resistance mechanisms and identifies potential new antifungal targets.
  • Published in:Mycology,
  • Study Type:Experimental Laboratory Study,
  • Source: PMID: 40083420, DOI: 10.1080/21501203.2024.2342521
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