Overexpression of the YAP1, PDE2, and STB3 genes enhances the tolerance of yeast to oxidative stress induced by 7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine.
7-chlorotetrazolo[5,1-c]benzo[1,2,4]triazine (CTBT) is an antifungal agent that induces oxidative stress and enhances the activity of other antifungals with different modes of action. A genome-wide screening of Saccharomyces cerevisiae genomic library in the high-copy-number plasmid revealed three genes, YAP1, PDE2, and STB3, which increased the CTBT tolerance of the parental strain. The YAP1 gene is known to activate many genes in response to oxidants. The PDE2 and STB3 genes encode the high-affinity cAMP phosphodiesterase and the transcription factor recognizing the ribosomal RNA processing element in promoter sequences, respectively. The protective effects of their overexpression against CTBT toxicity was observed in the absence of certain proteins involved in stress responses, cell wall integrity signaling, and chromatin remodeling. The enhanced CTBT tolerance of the YAP1, PDE2, and STB3 transformants was a consequence of their high antioxidant enzyme activities at the beginning of CTBT treatment in comparison with that of the parental strain, for that they inactivated the CTBT-induced reactive oxygen species. These results point to the complex interplay among the oxidant sensing, cAMP-protein kinase A signaling, and transcription reprogramming of yeast cells, leading to their better adaptation to the stress imposed by CTBT.
Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Slovak Republic.
Eva
E
Drobna
Zoltan
Z
Gazdag
Hana
H
Culakova
Vladimira
V
Dzugasova
Yvetta
Y
Gbelska
Miklos
M
Pesti
Julius
J
Subik
D000935:Antifungal Agents / Q000494:pharmacology; D065150:Cellular Reprogramming; D004271:DNA, Fungal / Q000235:genetics; D004361:Drug Tolerance; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*
C518245:7-chlorotetrazolo(5,1-c)benzo(1,2,4)triazine; D000935:Antifungal Agents; D004271:DNA, Fungal; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; C523898:Stb3 protein, S cerevisiae; D015534:Trans-Activators; D014157:Transcription Factors; D014227:Triazines; C086677:YAP1 protein, S cerevisiae