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

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.