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

Mushrooms are known not only for their taste but also for beneficial effects on health attributed to plethora of constituents. All mushrooms belong to the kingdom of fungi, which also includes yeasts and molds. Each year, hundreds of new metabolites of the main fungal sterol, ergosterol, are isolated from fungal sources. As a rule, further testing is carried out for their biological effects, and many of the isolated compounds exhibit one or another activity. This study aims to review recent literature (mainly over the past 10 years, selected older works are discussed for consistency purposes) on the structures and bioactivities of fungal metabolites of ergosterol. The review is not exhaustive in its coverage of structures found in fungi. Rather, it focuses solely on discussing compounds that have shown some biological activity with potential pharmacological utility.

• Klíčová slova
• anticancer, antiviral, cytotoxicity, ergosteroids, ergosterol, fungi, mushrooms,
• MeSH
• Agaricales * MeSH
• ergosterol * analogy a deriváty   metabolismus   farmakologie   MeSH
• houby metabolismus   MeSH
• steroidy metabolismus   farmakologie   MeSH
• steroly metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ergostane MeSH Prohlížeč
• ergosterol * MeSH
• steroidy MeSH
• steroly MeSH

Biological membranes are tricky to investigate. They are complex in terms of molecular composition and structure, functional over a wide range of time scales, and characterized by nonequilibrium conditions. Because of all of these features, simulations are a great technique to study biomembrane behavior. A significant part of the functional processes in biological membranes takes place at the molecular level; thus computer simulations are the method of choice to explore how their properties emerge from specific molecular features and how the interplay among the numerous molecules gives rise to function over spatial and time scales larger than the molecular ones. In this review, we focus on this broad theme. We discuss the current state-of-the-art of biomembrane simulations that, until now, have largely focused on a rather narrow picture of the complexity of the membranes. Given this, we also discuss the challenges that we should unravel in the foreseeable future. Numerous features such as the actin-cytoskeleton network, the glycocalyx network, and nonequilibrium transport under ATP-driven conditions have so far received very little attention; however, the potential of simulations to solve them would be exceptionally high. A major milestone for this research would be that one day we could say that computer simulations genuinely research biological membranes, not just lipid bilayers.

• MeSH
• biologické modely * MeSH
• fosfolipidy chemie   metabolismus   MeSH
• kyseliny karboxylové chemie   metabolismus   MeSH
• lidé MeSH
• lipidomika metody   MeSH
• membránové lipidy chemie   metabolismus   MeSH
• membrány chemie   metabolismus   fyziologie   MeSH
• počítačová simulace MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfolipidy MeSH
• kyseliny karboxylové MeSH
• membránové lipidy MeSH

We investigated the impact of the deletions of genes from the final steps in the biosynthesis of ergosterol (ERG6, ERG2, ERG3, ERG5, ERG4) on the physiological function of the Saccharomyces cerevisiae plasma membrane by a combination of biological tests and the diS-C3(3) fluorescence assay. Most of the erg mutants were more sensitive than the wild type to salt stress or cationic drugs, their susceptibilities were proportional to the hyperpolarization of their plasma membranes. The different sterol composition of the plasma membrane played an important role in the short-term and long-term processes that accompanied the exposure of erg strains to a hyperosmotic stress (effect on cell size, pH homeostasis and survival of yeasts), as well as in the resistance of cells to antifungal drugs. The pleiotropic drug-sensitive phenotypes of erg strains were, to a large extent, a result of the reduced efficiency of the Pdr5 efflux pump, which was shown to be more sensitive to the sterol content of the plasma membrane than Snq2p. In summary, the erg4Δ and erg6Δ mutants exhibited the most compromised phenotypes. As Erg6p is not involved in the cholesterol biosynthetic pathway, it may become a target for a new generation of antifungal drugs.

• MeSH
• ABC transportéry genetika   metabolismus   MeSH
• antifungální látky farmakologie   MeSH
• biosyntetické dráhy genetika   MeSH
• buněčná membrána chemie   fyziologie   MeSH
• ergosterol biosyntéza   chemie   MeSH
• flukonazol farmakologie   MeSH
• fluorescenční mikroskopie MeSH
• koncentrace vodíkových iontů MeSH
• membránové potenciály fyziologie   MeSH
• methyltransferasy genetika   metabolismus   MeSH
• mnohočetná fungální léková rezistence účinky léků   genetika   fyziologie   MeSH
• molekulární struktura MeSH
• mutace MeSH
• Saccharomyces cerevisiae - proteiny genetika   metabolismus   MeSH
• Saccharomyces cerevisiae chemie   genetika   fyziologie   MeSH
• tolerance k soli genetika   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ABC transportéry MeSH
• antifungální látky MeSH
• delta 24-sterol methyltransferase MeSH Prohlížeč
• ergosterol MeSH
• flukonazol MeSH
• methyltransferasy MeSH
• PDR5 protein, S cerevisiae MeSH Prohlížeč
• Saccharomyces cerevisiae - proteiny MeSH
• SNQ2 protein, S cerevisiae MeSH Prohlížeč