Browsing by Author "Tsao, Ming-Yang"

Now showing 1 - 2 of 2

Cph1p negatively regulates MDR1 involved in drug resistance in Candida albicans
(2015-06-01)
Lo, Hsiu Jung
;
Tseng, Kuo-Yun
;
Kao, Yeong-Yi
;
Tsao, Ming-Yang
;
Lo, Han-Lun
The cph1/cph1 efg1/efg1 double mutant in Candida albicans is defective in filamentous growth and is avirulent in a mouse model. We previously reported that Efg1p but not Cph1p is involved in drug resistance by negatively regulating ERG3 in C. albicans. In the current study, we have found that overexpression of 0411 in Saccharomyces cerevisiae increases susceptibility to the antifungal drug fluconazole. Furthermore, in C. albicans, null mutation of 0411 increased the expression of MDR1 as well as decreased susceptibility to fluconazole and voriconazole but not to amphotericin B. These findings indicate that although Efg1p and Cph1p may have the same effects on virulence, they have opposite effects on drug resistance in C. albicans. (C) 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Serum repressing efflux pump CDR1 in Candida albicans
(2006-07-13)
Yang, Yun-Liang
;
Lin, Yi-Hsuan
;
Tsao, Ming-Yang
;
Chen, Chia-Geun
;
Shih, Hsin-I
Background: In the past decades, the prevalence of candidemia has increased significantly and drug resistance has also become a pressing problem. Overexpression of CDR1, an efflux pump, has been proposed as a major mechanism contributing to the drug resistance in Candida albicans. It has been demonstrated that biological fluids such as human serum can have profound effects on antifungal pharmacodynamics. The aim of this study is to understand the effects of serum in drug susceptibility via monitoring the activity of CDR1 promoter of C. albicans. Results: The wild-type C. albicans cells ( SC5314) but not the cdr1/cdr1 mutant cells became more susceptible to the antifungal drug when the medium contained serum. To understand the regulation of CDR1 in the presence of serum, we have constructed CDR1 promoter-Renilla luciferase ( CDR1p-RLUC) reporter to monitor the activity of the CDR1 promoter in C. albicans. As expected, the expression of CDR1p-RLUC was induced by miconazole. Surprisingly, it was repressed by serum. Consistently, the level of CDR1 mRNA was also reduced in the presence of serum but not N-acetyl-D-glucosamine, a known inducer for germ tube formation. Conclusion: Our finding that the expression of CDR1 is repressed by serum raises the question as to how does CDR1 contribute to the drug resistance in C. albicans causing candidemia. This also suggests that it is important to re-assess the prediction of in vivo therapeutic outcome of candidemia based on the results of standard in vitro antifungal susceptibility testing, conducted in the absence of serum.