MYCOLab Ai Logo - gold and army green

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

Summary

Researchers discovered that a gene called ctf1 in a harmful fungus called Aspergillus fumigatus helps control how resistant the fungus is to antifungal medications like voriconazole. When this gene is removed, the fungus becomes more resistant to these drugs because it pumps them out more efficiently. Understanding this mechanism could help doctors develop better treatments for serious fungal infections in vulnerable patients.

Background

Aspergillus fumigatus is a major cause of opportunistic mold infections in immunocompromised individuals with high morbidity and mortality rates. Antifungal resistance, particularly to triazoles, presents a significant clinical challenge. Understanding the mechanisms of azole resistance is crucial for developing new treatment strategies.

Objective

To investigate the function of ctf1 (AFUA_1G03800), a C6 zinc finger transcription factor gene, in A. fumigatus azole resistance mechanisms. The study aimed to elucidate how ctf1 deletion affects antifungal susceptibility and virulence factors.

Results

ctf1 deletion resulted in 2-fold decreased susceptibility to voriconazole and inhibited fungal growth with reduced conidial production. Decreased antifungal sensitivity was associated with increased ergosterol content and significant upregulation of mdr1, mdr2, and mdr4 efflux pump genes, while cyp51A and cyp51B expression remained unchanged.

Conclusion

ctf1 is a novel C6 transcription factor essential for maintaining normal voriconazole sensitivity in A. fumigatus. The decreased azole sensitivity in ctf1-deficient strains is primarily mediated through increased drug efflux via ABC transporters, independent of ergosterol biosynthesis enzyme expression, contributing to understanding of A. fumigatus resistance mechanisms.
  • Published in:Mycology,
  • Study Type:Experimental Research Study,
  • Source: PMID: 40083420, DOI: 10.1080/21501203.2024.2342521
Scroll to Top