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Clinical and Genomic Insights into Antifungal Resistance in Aspergillus Isolates from Thailand

Summary

Researchers in Thailand found that certain fungal infections caused by Aspergillus fumigatus are becoming resistant to common antifungal medications like voriconazole. They identified a specific genetic mutation called TR34/L98H in one patient sample that makes the fungus resistant to azole drugs used to treat these serious infections. By analyzing the genetic makeup of these resistant fungi, scientists discovered additional changes beyond the known resistance gene, suggesting these organisms may adapt in multiple ways to survive treatment. This is the first time this particular resistance mutation has been detected in a clinical patient sample in Thailand, indicating that antifungal resistance in Aspergillus is spreading and requires closer monitoring and testing.

Background

Aspergillus species are major opportunistic pathogens causing invasive aspergillosis with increasing antifungal resistance worldwide. Azole antifungals are first-line treatments, but resistance mechanisms including cyp51A mutations pose significant clinical challenges. This study investigates antifungal resistance patterns in Aspergillus isolates from a tertiary hospital in Thailand.

Objective

To characterize antifungal susceptibility and genomic features of Aspergillus isolates from sterile clinical specimens collected at a Thai tertiary hospital during 2023. The study aimed to identify resistance mechanisms and provide molecular insights into azole resistance in the region.

Results

Aspergillus fumigatus was the most frequent species (54%), followed by A. flavus (29%). Two A. fumigatus isolates showed elevated voriconazole MICs (2-4 µg/mL). One isolate (CUAFU23) was confirmed to harbor the TR34/L98H cyp51A mutation, marking the first clinical identification of this resistance mechanism in Thailand. Genomic profiling revealed distinct protein domain differences in the resistant strain compared to susceptible isolates.

Conclusion

The study demonstrates the emergence of azole-resistant A. fumigatus in Thailand, with TR34/L98H being a key resistance mechanism. Genomic profiling revealed broader adaptive changes beyond cyp51A mutations in resistant isolates. Integration of antifungal susceptibility testing, molecular diagnostics, and genomic analysis is essential for guiding effective treatment strategies and mitigating resistance spread.
  • Published in:Microorganisms,
  • Study Type:Clinical Cross-sectional Study,
  • Source: PMID: 41304180, DOI: 10.3390/microorganisms13112495
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