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Published on: June 13, 2021
CaNdt80 is involved in drug resistance in Candida albicans by regulating CDR1
Chia-Geun Chen1, Yun-Liang Yang, Hsin-I Shih
1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Abstract:
Overexpression of CDR1, an efflux pump, is one of the major mechanisms contributing to drug resistance in Candida albicans. CDR1 p-lacZ was constructed and transformed into a Saccharomyces cerevisiae strain so that the lacZ gene could be used as the reporter to monitor the activity of the CDR1 promoter. Overexpression of CaNDT80, the C. albicans homolog of S. cerevisiae NDT80, increases the beta-galactosidase activity of the CDR1 p-lacZ construct in S. cerevisiae. Furthermore, mutations in CaNDT80 abolish the induction of CDR1 expression by antifungal agents in C. albicans. Consistently, the Candt80/Candt80 mutant is also more susceptible to antifungal drugs than the wild-type strain. Thus, the gene for CaNdt80 may be the first gene among the regulatory factors involved in drug resistance in C. albicans whose function has been identified.
Insights
The study identifies CaNdt80 as a key regulator of drug resistance in Candida albicans. This transcription factor controls the expression of the CDR1 efflux pump, impacting antifungal drug susceptibility.
Area of Science:
- Molecular Biology
- Mycology
- Antimicrobial Resistance
Background:
- Overexpression of the CDR1 efflux pump is a primary mechanism of antifungal drug resistance in Candida albicans.
- Understanding the regulatory factors controlling CDR1 expression is crucial for developing strategies to combat drug resistance.
Purpose of the Study:
- To investigate the role of CaNDT80, a homolog of Saccharomyces cerevisiae NDT80, in regulating CDR1 expression and drug resistance in Candida albicans.
- To identify the first regulatory gene involved in Candida albicans drug resistance.
Main Methods:
- Constructed a CDR1 promoter-lacZ reporter system in Saccharomyces cerevisiae to monitor CDR1 promoter activity.
- Assessed the effect of CaNDT80 overexpression on beta-galactosidase activity.
- Generated CaNDT80 mutants in Candida albicans to study the induction of CDR1 expression by antifungal agents and drug susceptibility.
Main Results:
- Overexpression of CaNDT80 significantly increased beta-galactosidase activity, indicating enhanced CDR1 promoter activity.
- Mutations in CaNDT80 abolished the induction of CDR1 expression by antifungal agents in Candida albicans.
- Candida albicans strains with CaNDT80 mutations exhibited increased susceptibility to antifungal drugs compared to wild-type strains.
Conclusions:
- CaNDT80 is a critical regulatory factor that controls the expression of the CDR1 efflux pump in Candida albicans.
- CaNDT80 plays a significant role in mediating antifungal drug resistance in Candida albicans.
- The gene for CaNdt80 represents the first identified regulatory factor contributing to drug resistance in Candida albicans.
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