Detection of ERG11 gene mutation in coding and non-coding regions of clinical Candida glabrata (Nakaseomyces glabratus) isolates from Pakistan

Summary

Researchers in Pakistan identified genetic mutations in a dangerous fungus called Candida glabrata that makes it resistant to azole drugs, which are commonly used to treat fungal infections. They examined eight clinical samples and found novel mutations in the ERG11 gene, particularly in the promoter region of resistant strains. These findings suggest that the fungus may be developing new ways to survive azole treatment, which has important implications for patient treatment strategies.

Background

Candida glabrata (Nakaseomyces glabratus) is a common agent of invasive candidiasis with reduced susceptibility to azoles. Azole resistance arises through various mechanisms including ERG11 gene mutations, which encodes the key enzyme lanosterol 14α-demethylase involved in ergosterol biosynthesis.

Objective

To identify and characterize mutations in the coding and non-coding regions of the ERG11 gene in clinical isolates of C. glabrata (N. glabratus) from Pakistan. This is the first study evaluating ERG11 mutations in this species from Pakistan.

Results

A novel nucleotide change at c.-66 T/G upstream of the start codon ATG in the promoter region was identified in one fluconazole-resistant isolate. Two novel synonymous mutations (T300C and T834C) and previously reported synonymous mutations (T768C, A1023G, T1557A, A1581G) were detected. No non-synonymous mutations were found in the coding region.

Conclusion

This is the first study of ERG11 mutations in N. glabratus from Pakistan. The clinical significance of the uncommon c.-66 T/G mutation should be explored further through correlation with treatment outcomes. Larger genomic surveillance studies and investigation of other resistance mechanisms are recommended.
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