Nejvíce citovaný článek - PubMed ID 30398655
Erg6 gene is essential for stress adaptation in Kluyveromyces lactis
The ERG6 gene is crucial for the biosynthesis of ergosterol, a key component of yeast cell membranes. Our study examines the impact of ERG6 gene deletion on the membrane composition and physicochemical properties of the pathogenic yeast Candida glabrata. Specifically, we investigated changes in selected sterol content, phospholipid composition, transmembrane potential, and PDR16 gene activity. Sterol levels were measured using high-performance liquid chromatography, the phospholipid profile was analysed via thin-layer chromatography, transmembrane potential was assessed with fluorescence spectroscopy, and gene expression levels were determined by quantitative PCR. Our findings revealed a depletion of ergosterol, increased zymosterol and eburicol content, an increased phosphatidylcholine and a reduced phosphatidylethanolamine content in the Δerg6 strain compared to the wt. Additionally, the Δerg6 strain exhibited membrane hyperpolarization without changes in PDR16 expression. Furthermore, the Δerg6 strain showed increased sensitivity to the antifungals myriocin and aureobasidine A. These results suggest that ERG6 gene deletion leads to significant alterations in membrane composition and may activates an alternative ergosterol synthesis pathway in the C. glabrata Δerg6 deletion mutant.
- Klíčová slova
- Candida glabrata, ERG6, Eburicol, Ergosterol, Phospholipids, Transmembrane potential,
- MeSH
- antifungální látky farmakologie MeSH
- buněčná membrána * metabolismus chemie účinky léků MeSH
- Candida glabrata * genetika metabolismus účinky léků cytologie MeSH
- delece genu * MeSH
- ergosterol metabolismus biosyntéza MeSH
- fosfolipidy metabolismus MeSH
- fungální proteiny * genetika metabolismus MeSH
- membránové potenciály účinky léků MeSH
- regulace genové exprese u hub MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antifungální látky MeSH
- ergosterol MeSH
- fosfolipidy MeSH
- fungální proteiny * MeSH
KlUpc2p, a transcription factor belonging to the fungal binuclear cluster family, is an important regulator of ergosterol biosynthesis and azole drug resistance in Kluyveromyces lactis. In this work, we show that the absence of KlUpc2p generates Rag- phenotype and modulates the K. lactis susceptibility to oxidants and calcofuor white. The KlUPC2 deletion leads to increased expression of KlMGA2 gene, encoding an important regulator of hypoxic and lipid biosynthetic genes in K. lactis and also KlHOG1 gene. The absence of KlUpc2p does not lead to statistically significant changes in glycerol, corroborating the expression of KlGPD1 gene, encoding NAD+-dependent glycerol-3-phosphate dehydrogenase, that is similar in both the deletion mutant and the parental wild-type strain. Increased sensitivity of Klupc2 mutant cells to brefeldin A accompanied with significant increase in KlARF2 gene expression point to the involvement of KlUpc2p in intracellular signaling. Our observations highlight the connections between ergosterol and fatty acid metabolism to modulate membrane properties and point to the possible involvement of KlUpc2p in K. lactis oxidative stress response.
- Klíčová slova
- Ergosterol, Kluyveromyces lactis, Lipid trafficking, Oxidative stress, Susceptibility, UPC2,
- MeSH
- delece genu MeSH
- ergosterol metabolismus MeSH
- fungální proteiny * genetika metabolismus MeSH
- Kluyveromyces * genetika metabolismus MeSH
- regulace genové exprese u hub MeSH
- transkripční faktory genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ergosterol MeSH
- fungální proteiny * MeSH
- transkripční faktory MeSH