Comparative Analysis of CDR1 Gene Deletion Effects on Fluconazole Susceptibility in Candida glabrata and Candida albicans

Abstract

Background: CDR1 is an important component of ATP-binding cassette (ABC) transporters, functioning as an efflux pump that enables different Candida species to develop resistance to the antifungal drug fluconazole. Aim: To investigate the effect of CDR1 gene deletion on fluconazole sensitivity in Candida glabrata and Candida albicans. Methods: Antifungal resistance was assessed using gene knockout assays. Broth microdilution techniques were applied, and IC₅₀ values were calculated to evaluate changes in drug susceptibility. Results: CDR1 deletion mutants in both species exhibited markedly increased sensitivity to fluconazole. However, resistance patterns differed between the two species. For C. glabrata, MIC decreased from >200 mg/L to 1.5–6 mg/L and IC₅₀ reduced to ~2.5 mg/L. For C. albicans, MIC decreased from >200 mg/L to 0.5–1 mg/L and IC₅₀ reduced to ~0.8 mg/L. Overall, susceptibility increased by more than 80-fold in C. glabrata and over 100-fold in C. albicans. Conclusion: CDR1 acts as a major determinant of fluconazole resistance in both C. glabrata and C. albicans. Its role varies between species, highlighting the importance of considering CDR1 as a key regulatory mechanism and a target for species-specific antifungal therapy.