Identification of Genomic Binding Sites for Candida glabrata Pdr1 Transcription Factor in Wild-Type and ρ 0 Cells
| Autor: | W. Scott Moye-Rowley, Thomas B. Bair, Sanjoy Paul |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Antifungal Agents
Antifungal drug Candida glabrata Locus (genetics) Microbiology Fungal Proteins Mechanisms of Resistance Drug Resistance Fungal Pharmacology (medical) Candida albicans Fluconazole Gene Pharmacology Genetics Fungal protein Binding Sites Base Sequence biology Candidiasis High-Throughput Nucleotide Sequencing Promoter Sequence Analysis DNA biology.organism_classification Mitochondria DNA-Binding Proteins Infectious Diseases ATP-Binding Cassette Transporters Chromatin immunoprecipitation Transcription Factors |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 58:6904-6912 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.03921-14 |
| Popis: | The fungal pathogen Candida glabrata is an emerging cause of candidiasis in part owing to its robust ability to acquire tolerance to the major clinical antifungal drug fluconazole. Similar to the related species Candida albicans , C. glabrata most typically gains azole tolerance via transcriptional induction of a suite of resistance genes, including a locus encoding an ABCG-type ATP-binding cassette (ABC) transporter that is referred to as CDR1 in Candida species. In C. glabrata , CDR1 expression is controlled primarily by the activity of a transcriptional activator protein called Pdr1. Strains exhibiting reduced azole susceptibility often contain substitution mutations in PDR1 that in turn lead to elevated mRNA levels of target genes with associated azole resistance. Pdr1 activity is also induced upon loss of the mitochondrial genome status and upon challenge by azole drugs. While extensive analyses of the transcriptional effects of Pdr1 have identified a number of genes that are regulated by this factor, we cannot yet separate direct from indirect target genes. Here we used chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-seq) to identify the promoters and associated genes directly regulated by Pdr1. These genes include many that are shared with the yeast Saccharomyces cerevisiae but others that are unique to C. glabrata , including the ABC transporter-encoding locus YBT1 , genes involved in DNA repair, and several others. These data provide the outline for understanding the primary response genes involved in production of Pdr1-dependent azole resistance in C. glabrata . |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|