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Updated: Jul 3, 2026

Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
RTA2, a novel gene involved in azole resistance in Candida albicans
Xin-Ming Jia1, Zhi-Ping Ma, Yu Jia
1Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Abstract:
Widespread and repeated use of azoles, particularly fluconazole, has led to the rapid development of azole resistance in Candida albicans. Overexpression of CDR1, CDR2, and CaMDR1 has been reported contributing to azole resistance in C. albicans. In this study, hyper-resistant C. albicans mutant, with the above three genes deleted, was obtained by exposure to fluconazole and fluphenezine for 28 passages. Thirty-five differentially expressed genes were identified in the hyper-resistant mutant by microarray analysis; among the 13 up-regulated genes, we successfully constructed the rta2 and ipf14030 null mutants in C. albicans strain with deletions of CDR1, CDR2 and CaMDR1. Using spot dilution assay, we demonstrated that the disruption of RTA2 increased the susceptibility of C. albicans to azoles while the disruption of IPF14030 did not influence the sensitivity of C. albicans to azoles. Meanwhile, we found that ectopic overexpression of RTA2 in C. albicans strain with deletions of CDR1, CDR2 and CaMDR1 conferred resistance to azoles. RTA2 expression was found elevated in clinical azole-resistant isolates of C. albicans. In conclusion, our findings suggest that RTA2 is involved in the development of azole resistance in C. albicans.
Insights
The gene RTA2 is implicated in azole resistance in Candida albicans. Disrupting RTA2 increases susceptibility to azoles, while its overexpression confers resistance, suggesting RTA2
Area of Science:
- Mycology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Widespread azole use, especially fluconazole, drives resistance in Candida albicans.
- Overexpression of CDR1, CDR2, and CaMDR1 genes contributes to azole resistance.
Purpose of the Study:
- To investigate novel genes involved in azole resistance in Candida albicans.
- To identify and characterize genes contributing to hyper-resistance in Candida albicans mutants.
Main Methods:
- Generated a hyper-resistant Candida albicans mutant by serial passage with fluconazole and fluphenezine.
- Utilized microarray analysis to identify differentially expressed genes in the resistant mutant.
- Constructed and analyzed null mutants for RTA2 and IPF14030, and overexpressed RTA2.
Main Results:
- Disruption of RTA2 increased Candida albicans susceptibility to azoles.
- Disruption of IPF14030 did not affect azole sensitivity.
- Ectopic overexpression of RTA2 conferred azole resistance.
- RTA2 expression was elevated in clinical azole-resistant isolates.
Conclusions:
- RTA2 plays a significant role in the development of azole resistance in Candida albicans.
- RTA2 is a potential therapeutic target for overcoming azole resistance.
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