Characterization of the zinc cluster transcription factor Rds2 in Saccharomyces cerevisiae links glucose metabolism to antifungal drug resistance

Full title: 

Characterization of the zinc cluster transcription factor Rds2 in Saccharomyces cerevisiae links glucose metabolism to antifungal drug resistance

Author: 

Mitra, Shuvadeep

Year: 

2011

Reference type: 

Thesis

ISBN/ISSN: 

9780494759264

Abstract: 

In Saccharomyces cerevisiae, zinc cluster proteins constitute the major family of transcriptional regulators for a variety of metabolic processes, yet the function of many are currently unknown. Previous studies have characterized Rds2 as a zinc cluster transcription factor that plays a role in antifungal drug resistance, but an exact mechanism is undefined. However, it has been established that Rds2 is a major regulator of gluconeogenesis. In this study, we aim to further mechanistically characterize the role of Rds2 in antifungal drug resistance. Microarray-based expression profiling of both wild type and 916;rds2 strains treated with ketoconazole indicates a greater than 2-fold decreased expression of genes involved in gluconeogenesis and the glyoxylate cycle, such as PCK1, YIG1, and MLS1, in cells lacking Rds2. Quantitative real-time polymerase chain reaction (qPCR) confirmed our microarray data. Furthermore, deletion of these metabolic genes confers azole hypersensitivity. Our preliminary results show that Rds2's role as a regulator of gluconeogenesis and the glyoxylate cycle is linked to its role in antifungal drug resistance.