title: Stress response and expression of fluconazole resistance associated genes in the pathogenic yeast Candida glabrata deleted in the CgPDR16 gene.
abstract: In yeasts, the PDR16 gene encodes a phosphatidylinositol transfer protein which belongs to the Sec14 homologue (SFH) family and localizes to lipid droplets, microsomes and at the cell periphery. The loss of its function alters the lipid droplet metabolism and plasma membrane properties, and renders yeast cells more sensitive to azole antimycotics. In this study, the entire chromosomal CgPDR16 ORF was replaced by the ScURA3 gene both in azole sensitive and azole resistant strains of Candida glabrata bearing a gain-of-function mutation in the CgPDR1 gene, and their responses to different stresses were assessed. The CgPDR16 deletion was found to sensitize the mutant strains to azole antifungals without changes in their osmo- and halotolerance. Fluconazole treated pdr16Δ mutant strains displayed a reduced expression of several genes involved in azole tolerance. The gain-of-function CgPDR1 allele as well as the cycloheximide and hydrogen peroxide treatments of cells enhanced the expression of the CgPDR16 gene. The results indicate that CgPDR16 belongs to genes whose expression is induced by chemical and oxidative stresses. The loss of its function can attenuate the expression of drug efflux pump encoding genes that might also contribute to the decreased azole tolerance in pdr16Δ mutant cells.
authors.affiliation: Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovak Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Culakova
authors.affiliation: Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovak Republic.
authors.forename: Vladimira
authors.initials: V
authors.lastname: Dzugasova
authors.affiliation: Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovak Republic.
authors.forename: Romana
authors.initials: R
authors.lastname: Valencikova
authors.affiliation: Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovak Republic.
authors.forename: Yvetta
authors.initials: Y
authors.lastname: Gbelska
authors.affiliation: Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovak Republic. Electronic address: subik.julius@gmail.com.
authors.forename: Julius
authors.initials: J
authors.lastname: Subik
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism*; D041221:Candida glabrata / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D008826:Microbial Sensitivity Tests; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D000935:Antifungal Agents; D049294:Phospholipid Transfer Proteins; D015725:Fluconazole
keywords: Azole antimycotics; CgPDR16; Drug resistance; Gene expression; Halotolerance