Importance and Role of Sterols in Fungal Membranes

Bossche, H. Vanden

doi:10.1007/978-3-642-74215-6_10

Cited by 51 publications

(33 citation statements)

References 99 publications

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“…However, although glucose consumption was identical in both sets of shake flasks, the increase in ergosterol concentration was slower in the unbaffled flasks. Ergosterol synthesis requires molecular oxygen (18), and low oxygen tensions can dramatically reduce ergosterol content in Mucor rouxii (15) and Rhizopus oligosporus (14). In our study, oxygen levels were similar in both baffled and unbaffled shake flasks.…”

Section: Discussionsupporting

confidence: 52%

“…In several species of aquatic hyphomycete cultured in liquid media with different C/N ratios, ergosterol content was only slightly affected by culture age and medium composition (8). However, other factors also can influence ergosterol synthesis (18,19). In particular, ergosterol synthesis requires molecular oxygen, and low oxygen tensions can dramatically reduce ergosterol concentration (14, 15).…”

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confidence: 99%

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Effect of Culture Conditions on Ergosterol as an Indicator of Biomass in the Aquatic Hyphomycetes

Charcosset¹,

Chauvet²

2001

Appl Environ Microbiol

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Ergosterol is a membrane component specific to fungi that can be used to estimate fungal biomass using appropriate factors of conversion. Our objectives were to determine the limits of use of ergosterol content as a measure of biomass for aquatic hyphomycetes, and to evaluate a previously established ergosterol-to-biomass conversion factor. We varied inoculum quality, growth medium, and degree of shaking of four aquatic hyphomycete species. In cultures inoculated with homogenized mycelium, we found a significant effect of shaking condition and culture age on ergosterol content. In liquid cultures with defined medium, ergosterol content reached 10 to 11 g/mg of mycelium (dry mass) and varied by factors of 2.2 during exponential growth and 1.3 during stationary phase. The increase in ergosterol content during exponential phase could be attributed, at least in part, to rapid depletion of glucose. Oxygen availability to internal hyphae within the mycelial mass is also responsible for the differences found between culture conditions. Ergosterol concentration ranged from 0.8 to 1.6 g/mg in static cultures inoculated with agar plugs. Ergosterol content varied by a factor of 4 in two media of different richnesses. For different combinations of these parameters, strong (r 2 ‫؍‬ 0.83 to 0.98) and highly significant (P Ӷ 0.001) linear relationships between ergosterol and mycelial dry mass (up to 110 mg) were observed. Overall, the ergosterol content varied by a factor of 14 (0.8 to 11 mg/g). These results suggest that care must be taken when the ergosterol content is used to compare data generated in different field environments.Ergosterol is a membrane component of most fungi but is absent from vascular plants and metazoan animals (13). Its relative chemical instability suggests that it is rapidly degraded upon cell death and therefore provides a good quantitative measure of viable cells (19). Hence, ergosterol levels are commonly used to estimate fungal biomass on various substrates under a wide range of field and environmental conditions (4,6,9,10,11,20).Estimates of the importance of aquatic hyphomycetes have increased. Based on ergosterol and ATP assays, the biomass of these fungi is estimated to constitute up to 16% of the detrital dry mass of decomposing leaf litter (6). These estimates rely on conversion factors to estimate the amount of fungal biomass and are based on the amount of ergosterol measured. The accuracy of these conversion factors is critical, with values for aquatic hyphomycetes estimated to range from 2 to 16 g/mg (dry weight) (10). Based on liquid cultures of various species grown under laboratory conditions, a mean conversion factor of 5.5 g/mg of mycelium (dry mass) has been proposed (8).Ergosterol content depends on the physiological state and general growth conditions of the fungus. In several species of aquatic hyphomycete cultured in liquid media with different C/N ratios, ergosterol content was only slightly affected by culture age and medium composition (8). However, other factors also can i...

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Section: Discussionsupporting

confidence: 52%

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confidence: 99%

Effect of Culture Conditions on Ergosterol as an Indicator of Biomass in the Aquatic Hyphomycetes

Charcosset¹,

Chauvet²

2001

Appl Environ Microbiol

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“…On the basis of the proposition that mevinolin acts via a blockade of endogenous sterol synthesis at the level of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (1, 2, 13, 14; see below), we studied the effects of the action of this drug combined with other compounds that affect the same pathway but at a different step. Figure 2 shows the results of the combination of mevinolin with ketoconazole, a drug that blocks the cytochrome P-450-dependent demethylation of lanosterol (4,21,(40)(41)(42); while the drugs acting separately at 7.5 ,uM for mevinolin and 0.1 ,uM for ketoconazole produced just a moderate reduction (20 to 30%) in the growth rate, the drugs used in combination resulted in complete growth arrest followed by cell lysis (verified by light microscopy and trypan blue exclusion) at 144 h, essentially as was observed for the higher concentrations of mevinolin (Fig. 1).…”

Section: Methodsmentioning

confidence: 99%

“…One would also expect that this drug would function as a therapeutic agent in vivo, as a blockade of cholesterol synthesis in the host could be compensated for by dietary uptake, while the corresponding situation for the ergosterol-requiring parasites could not be expected. Moreover, as mevinolin acts at a point in the biosynthetic pathway different from that at which the specific ergosterol biosynthesis inhibitors act (30,31,34,(40)(41)(42), one would predict a mutual potentiation of their effects, based on previous studies (22,35,37). In this paper, we describe the effects of mevilonin on both proliferative stages of T. cruzi, epimastigotes and intracellular amastigotes in vitro and in a murine model of Chagas' disease and show that it indeed strongly potentiates the actions of ketoconazole and terbinafine in both binary and ternary combinations.…”

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confidence: 99%

Mevinolin (lovastatin) potentiates the antiproliferative effects of ketoconazole and terbinafine against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies

Urbina

Lazardi

Marchán

et al. 1993

Antimicrob Agents Chemother

112

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We have studied the antiproliferative effects of mevinolin (lovastatin), an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, on the protozoan parasite Trypanosoma (Schizotrypanum) cruzi and its ability to potentiate the action of specific ergosterol biosynthesis inhibitors, such as ketoconazole and terbinafine, both in vitro and in vivo. Against the epimastigote form in vitro, mevinolin produced a dose-dependent reduction of the growth rate up to 25 ,uM, but at 50 and 75 ,uM, complete growth arrest and cell lysis took place after 144 and 96 h, respectively. A systematic study of the effects of mevinolin combined with ketoconazole and terbinafine, which act at different points in the ergosterol biosynthesis pathway, on the proliferation of epimastigotes indicated a synergic action, as shown by concave isobolograms and fractional inhibitory concentration indexes ranging from 0.17 to 0.54. Analysis of the sterol composition and de novo sterol synthesis in control and treated cells by thin-layer and gas-liquid chromatographies showed that the antiproliferative effects of the drug alone and in combination were correlated with the depletion of the endogenous ergosterol pool and particularly with a critical (exogenous) cholesterol/endogenous 4-desmethyl sterol ratio in the cells. When we studied the effects of mevinolin on the amastigote form proliferating inside Vero cells in vitro, only very modest effects on the parasites were observed up to 0.75 ,M; above this concentration, significant deleterious effects on the host cells were found. However, when the same concentration of the drug was combined with ketoconazole, it was able to reduce by a factor of 10 the concentration of the azole required to eradicate the parasite (from 10 to 1 nM), again indicating a synergic action. On the other hand, a combination of mevinolin and terbinafine had only additive effects on amastigotes, but a ternary combination of mevinolin, ketoconazole, and terbinafine was again clearly synergistic. In vivo studies with a murine model of Chagas' disease showed that mevinolin can also potentiate the therapeutic effects of ketoconazole in this system; combined treatment with the two drugs at doses that alone offered only limited protection against the parasite was able to essentially eliminate circulating parasites and produce complete protection against death. These results confirm the synergic action against the proliferative stages of T. cruzi both in vitro and in vivo of combined ergosterol biosynthesis inhibitors that act at different points in the pathway and suggest that mevinolin combined with azoles, such as ketoconazole, can be used in the treatment of human Chagas' disease.

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“…Results on the influence of GRSP differ, so that the question is still unclear (Feeney et al, 2004;Young et al, 2012). Ergosterol is a specific component of fungal membranes and the major sterol in most filamentous fungi (Van den Bossche, 1990). It is recognized as being an important biomolecule through which reduced permeability may occur in a wide variety of biological surfaces/membranes (Young et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Biological and chemical factors controlling the patchy distribution of soil water repellency among plant species in a Mediterranean semiarid forest

et al. 2013

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Natural soil water repellency is a property that has already been observed in forest soils and is characterized by its patchydistribution. Ihere are many factors involved in its development. In this work, we have studied a large numberof chemical and biological factors underthe influence of differentplantspecies (Pinus halepensis, Quercus rotundifolia, Cistus albidus and Rosmarinus officinalis) to leam which has the greatest responsibility for its presence and persistence in the top-soillayer. We obselVed strong and significant correlations between ergosterol, giomalin related soil protein (GRSP), extractable lipids, soil organic matter (SOM) content and water repellency (WR). Our results suggested lipid fraction as the principal factor. Moreover, apart from Pinus, fungal biomass seems to be also related to the SOM content. Soil WR found under Pinus appears to be the most influenced by fungi. Quality of SOM, to be precise, lipid fraction could be responsible for WR and its relationship with fungal activity.

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Importance and Role of Sterols in Fungal Membranes

Cited by 51 publications

References 99 publications

Effect of Culture Conditions on Ergosterol as an Indicator of Biomass in the Aquatic Hyphomycetes

Effect of Culture Conditions on Ergosterol as an Indicator of Biomass in the Aquatic Hyphomycetes

Mevinolin (lovastatin) potentiates the antiproliferative effects of ketoconazole and terbinafine against Trypanosoma (Schizotrypanum) cruzi: in vitro and in vivo studies

Biological and chemical factors controlling the patchy distribution of soil water repellency among plant species in a Mediterranean semiarid forest

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