Journal Article

Functional characterization of the CgPGS1 gene reveals a link between mitochondrial phospholipid homeostasis and drug resistance in Candida glabrata

Batova, Monika, Dzugasova, Vladimira, Subik, Julius, Goffa, Eduard, Borecka-Melkusova, Silvia, Simockova, Maria

2008

Overview

Cardiolipin and its precursor phosphatidylglycerol are two anionic phospholipids that are essential for the biogenesis of functional mitochondria. To assess their role in mitochondrial and cellular functions in the pathogenic yeast Candida glabrata , a functional characterization of the CgPGS1 gene encoding the phosphatidylglycerolphosphate synthase has been carried out. Transposon insertion mutation in CgPGS1 resulted in the loss of phosphatidylglycerolphosphate synthase activity and in deficiency of both phosphatidylglycerol and cardiolipin. The Cgpgs1Δ mutant cells displayed reduced amounts of cytochrome b and cytochrome a , and had impaired growth on minimal media containing non-fermentable carbon and energy sources. They did not grow at elevated temperatures and failed to form colonies after induction of mitochondrial DNA deletions. The mutant cells also displayed a decreased susceptibility to fluconazole, ketoconazole, clotrimazole, voriconazole and posaconazole. In the Cgpgs1Δ mutant, a quantitative real time PCR revealed enhanced mRNA levels for multidrug resistance associated genes such as CgPDR1 encoding transcriptional activator and CgCDR1, CgPDH1 and CgSNQ2 coding for drug efflux transporters. These results indicate that CgPGS1 and anionic phospholipids are required for optimal mitochondrial functions and maintenance of yeast susceptibility to azole antifungals.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Biochemistry / Biomedical and Life Sciences / Biosynthesis / Candida glabrata / Candida glabrata - genetics / Candida glabrata - metabolism / carbon / Carbon sources / Cardiolipin / Cell Biology / Chromatography / Cloning, Molecular / Clotrimazole / Cytochrome / Cytochrome a / Cytochrome b / Cytochromes / Drug resistance / Drug Resistance, Fungal / Drug Resistance, Fungal - genetics / Efflux / energy / Energy sources / Evolution / Fluconazole / Functionals / Genes / Genetic Linkage / genetics / Genotype / Glucose / Glycerol / Heat resistance / High temperature / Homeostasis / Homeostasis - genetics / Intramolecular Oxidoreductases / Intramolecular Oxidoreductases - genetics / Intramolecular Oxidoreductases - metabolism / Ketoconazole / Kinases / Life Sciences / Lipids / Lipocalins / Lipocalins - genetics / Lipocalins - metabolism / messenger RNA / metabolism / Microbial Genetics and Genomics / Microbiology / Mitochondria / Mitochondria - genetics / Mitochondria - metabolism / Mitochondrial DNA / Multidrug resistance / multiple drug resistance / Mutant Proteins / Mutant Proteins - genetics / Mutant Proteins - metabolism / Mutants / Mutation / Phosphatidylglycerol / Phospholipids / Phospholipids - metabolism / Plant Sciences / Plasmids / polymerase chain reaction / Posaconazole / Proteomics / Research Article / temperature / transporters / transposons / Voriconazole / Yeast / Yeasts