Candida albicans and Candida glabrata clinical isolates exhibiting reduced echinocandin susceptibility

Area of Science:

• Mycology
• Antifungal Drug Resistance
• Molecular Biology

Background:

• Echinocandin drugs are crucial for treating fungal infections.
• Mutations in Candida albicans Gsc1 (Fks1) at residue S645 are a known cause of reduced echinocandin susceptibility (RES).
• Understanding resistance mechanisms is vital for effective antifungal therapy.

Purpose of the Study:

• To identify and characterize novel mutations associated with reduced echinocandin susceptibility (RES) in Candida species.
• To investigate the role of specific Fks protein residues in conferring RES.
• To explore the presence of similar resistance-conferring residues in other fungal species.

Main Methods:

• Genomic analysis of Candida albicans and Candida glabrata isolates exhibiting RES.
• Site-directed mutagenesis to introduce specific Fks2 mutations into susceptible C. glabrata strains.
• Comparative analysis of Fks protein sequences from various fungal species.

Main Results:

• A novel mutation, F641Y in C. albicans Fks1, was identified and associated with RES.
• The analogous mutation, F641V in C. glabrata Fks2, was confirmed to confer RES upon experimental introduction.
• Fks residues equivalent to Y641 were found in intrinsically RES Fusarium species and Candida guilliermondii.

Conclusions:

• The Fks1 residue F641 is a significant mutation site for reduced echinocandin susceptibility in Candida.
• The Fks2 residue F641 also plays a critical role in echinocandin resistance in Candida glabrata.
• The identification of similar residues in other fungal species suggests conserved mechanisms of echinocandin resistance.