The pel1 mutation in Saccharomyces cerevisiae and the Cgpgs1Delta mutation in Candida glabrata result in deficiency of mitochondrial phosphatidylglycerolphosphate synthase and lack of two anionic phospholipids, phosphatidylglycerol and cardiolipin. DNA sequence analysis of the PCR-amplified pel1 mutant allele revealed that the pel1 mutation resulted from a single amino-acid substitution (Glu(463)Lys) in the C-terminal part of encoded enzyme. The CgPGS1 gene cloned in a centromeric pFL38 vector functionally complemented the pel1 mutation in S. cerevisiae. Likewise, the ScPGS1 gene cloned in pCgACU5 plasmid fully complemented the Cgpgs1Delta mutation in C. glabrata. This mutation increased the cell surface hydrophobicity and decreased biofilm formation. These results support a close evolutionary relatedness of S. cerevisiae and C. glabrata and point to the relationship between expression of virulence factors and anionic phospholipid deficiency in pathogenic C. glabrata.

• MeSH
• Biofilms MeSH
• Phenotype MeSH
• Phospholipids chemistry   deficiency   MeSH
• Fungal Proteins chemistry   genetics   metabolism   MeSH
• Hydrophobic and Hydrophilic Interactions MeSH
• Yeasts chemistry   classification   genetics   physiology   MeSH
• Molecular Sequence Data MeSH
• Mutation * MeSH
• Amino Acid Sequence MeSH
• Sequence Alignment MeSH
• Transferases (Other Substituted Phosphate Groups) chemistry   genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase MeSH Browser
• Phospholipids MeSH
• Fungal Proteins MeSH
• Transferases (Other Substituted Phosphate Groups) MeSH

Decreased susceptibility of K. lactis mutants impaired in the function of cytochrome c, cytochrome c1 and cytochrome-c oxidase to fluconazole, bifonazole and amphotericin B in comparison with the isogenic wild-type strain was observed. Flow cytometry with rhodamine 6G did not show any changes in the accumulation of the dye in the mutant cells compared with the corresponding wild-type strain. Sterol analysis showed similar overall amount of sterols in both wild-type and mutant cells. Taking into account the increased amphotericin B resistance and significantly diminished susceptibility of mutant cells to lyticase digestion, the cell wall structure and/or composition may probably be responsible for the observed changes in the susceptibility of mutants to the antifungal compounds used.

• MeSH
• Amphotericin B pharmacology   MeSH
• Antifungal Agents pharmacology   MeSH
• Cell Wall chemistry   drug effects   MeSH
• Glucan Endo-1,3-beta-D-Glucosidase metabolism   MeSH
• Drug Resistance, Fungal * MeSH
• Fungal Proteins genetics   metabolism   MeSH
• Kluyveromyces cytology   drug effects   genetics   physiology   MeSH
• Microbial Sensitivity Tests MeSH
• Mitochondria drug effects   genetics   physiology   MeSH
• Multienzyme Complexes metabolism   MeSH
• Mutation * MeSH
• Blotting, Northern MeSH
• Peptide Hydrolases metabolism   MeSH
• Flow Cytometry MeSH
• Sterols metabolism   MeSH
• Electron Transport drug effects   genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Amphotericin B MeSH
• Antifungal Agents MeSH
• Glucan Endo-1,3-beta-D-Glucosidase MeSH
• Fungal Proteins MeSH
• lyticase MeSH Browser
• Multienzyme Complexes MeSH
• Peptide Hydrolases MeSH
• Sterols MeSH

Saccharomyces cerevisiae pell and crd1 mutants deficient in the biosynthesis of mitochondrial phosphatidylglycerol (PG) and cardiolipin (CL) as well as Kluyveromyces lactis mutants impaired in the respiratory chain function (RCF) containing dysfunctional mitochondria show altered sensitivity to metabolic inhibitors. The S. cerevisiae pell mutant displayed increased sensitivity to cycloheximide, chloramphenicol, oligomycin and the cell-wall perturbing agents caffeine, caspofungin and hygromycin. On the other hand, the pel1 mutant was less sensitive to fluconazole, similarly as the K. lactis mutants impaired in the function of mitochondrial cytochromes. Mitochondrial dysfunction resulting either from the absence of PG and CL or impairment of the RCF presumably renders the cells more resistant to fluconazole. The increased tolerance of K. lactis respiratory chain mutants to amphotericin B, caffeine and hygromycin is probably related to a modification of the cell wall.

• MeSH
• Antifungal Agents pharmacology   MeSH
• Cell Wall physiology   MeSH
• Phosphatidylglycerols genetics   metabolism   MeSH
• Drug Resistance, Fungal genetics   MeSH
• Cardiolipins genetics   metabolism   MeSH
• Kluyveromyces drug effects   genetics   MeSH
• Microbial Sensitivity Tests MeSH
• DNA, Mitochondrial genetics   MeSH
• Mitochondria genetics   physiology   MeSH
• Mutation MeSH
• Saccharomyces cerevisiae drug effects   genetics   MeSH
• Electron Transport * drug effects   genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antifungal Agents MeSH
• Phosphatidylglycerols MeSH
• Cardiolipins MeSH
• DNA, Mitochondrial MeSH