Lipid composition and polyene antibiotic resistance of Candida albicans mutants

1978 ◽  
Vol 56 (2) ◽  
pp. 135-142 ◽  
Author(s):  
A. M. Pierce ◽  
H. D. Pierce Jr. ◽  
A. M. Unrau ◽  
A. C. Oehlschlager

Four polyene-resistant mutants (C7, E4, C4, D10) of Candida albicans were derived by mutagenesis with N-methyl-N′-nitro-N-nitrosoguanidine followed by isolation on nystatin-containing medium. The mutants were cross resistant to amphotericin B, lucensomycin, and candicidin and showed the same order of increasing resistance to the four polyenes tested, i.e., C7 < E4 < C4 < D10. Free sterols, sterol esters, and phospholipid fatty acids were analyzed in the mutants and sensitive parent strain. The lipids of C7 were the same as those of the sensitive parent strain. Mutant E4 contained lichesterol and other Δ8-sterols indicating a block at the Δ8→ Δ7 isomerase, and most of the sterol ester fraction consisted of 4,14-desmethyl sterols. The most resistant mutants C4 and D10 had reduced growth rates, alterations in phospholipid fatty acids, and the absence of 4,14-desmethyl sterols. Mutants C4 and D10 had similar lipid compositions with 24-methylenelanosterol as the major sterol and lesser amounts of obtusifoliol and lanosterol. The proportion of the total sterol that was esterified was low and similar (19–34%) in cultures of the mutants and of the sensitive strain harvested in the same stage of stationary growth. Total sterol content, however, increased with resistance. Polyene resistance was better correlated with the type of sterols in the total sterol pools rather than with the degree of esterification of the individual sterols, i.e., resistance increased with the presence of Δ8- and 4,14-methyl sterols. Our data indicate that factors other than or in addition to alterations in sterol and phospholipid patterns account for polyene resistance.

1986 ◽  
Vol 51 (4) ◽  
pp. 948-955 ◽  
Author(s):  
Karel Stránský ◽  
Antonín Trka ◽  
Miloš Buděšínský ◽  
Milan Streibl

Surface and internal lipidic compounds from the springtail Tetrodontophora bielanensis (WAGA) were investigated. Using chromatographic and spectroscopic methods the following compounds were detected: n-alkanes (C15 - C35), lycopane (C40H82), olefin C40H80, seven groups of esters (including sterol esters), secondary alcohol C40H82O, triacyl glycerols, free saturated and unsaturated fatty acids (C12 - C22) and free sterols (cholesterol and desmosterol).


1979 ◽  
Vol 57 (2) ◽  
pp. 112-116 ◽  
Author(s):  
A. M. Pierce ◽  
H. D. Pierce Jr. ◽  
A. M. Unrau ◽  
A. C. Oehlschlager ◽  
R. E. Subden ◽  
...  

The composition of the free and esterified sterols in Neurospora crassa was examined as a function of incubation time in starvation medium containing [2-14C]mevalonic acid. The 14C incorporation was monitored in nuclear methylated and 4, 14-desmethyl sterol fractions. After 7 h incubation, sterol esterification had increased from an initial 5% in the log phase culture to 48% of the total sterol pool, with a concomitant decrease in free sterols. The relationship of the free and esterified sterol components in ergosterol biosynthesis is discussed.


1966 ◽  
Vol 21 (9) ◽  
pp. 859-867 ◽  
Author(s):  
Waldemar Eichenberger ◽  
Wilhelm Menke

The nature and quantity of sterols in leaves and chloroplasts of Spinacia oleracea, Antirrhinum majus, and Allium porrum were determined. From dried leaves 0.05 - 0.18% free and esterified sterols were isolated, and 0.04-0.09% from chloroplasts. Although approximately half the lipids of leaves is localized in chloroplasts we found no more than a quarter of leaf sterols in the chloroplasts. The mixture of sterols contains a major sterol and minor sterols in these species. In spinach a-spinasterol is the major sterol and in Antirrhinum and Allium β-sitosterol. Moreover, we established Δ7-stigmastenol and cholesterol in spinach. Besides for free sterols, leaves contain sterol esters and glycosides. Palmitic acid is the binding partner in the sterol esters of spinach, and glucose and mannose are the binding partners in sterol glycosides. Chloroplasts contain the same sterols as leaves do. Only a trace of sterol glycosides could be detected in chloroplast preparations.


HortScience ◽  
1995 ◽  
Vol 30 (2) ◽  
pp. 191b-191
Author(s):  
Bruce D. Whitaker

Altered metabolism of membrane lipids has been proposed as a mechanism for the beneficial effects of postharvest calcium treatment on apple quality. A previous study showed that after transfer of apples stored 6 months at 0C to 20C, calcium-treated fruit exhibited slower loss of galactolipid and altered levels of sterol conjugates. The present study of lipids in “control” fruit was conducted as a prelude to further in-depth analyses of the effects of postharvest calcium and heat treatments on lipid metabolism in apples during and after cold storage. Neutral lipid, glycolipid (GL), and phospholipid (PL) fractions were obtained by column chromatography followed by TLC separation of GL and PL classes. The major GL were steryl glycosides (SG), acylated steryl glycosides (ASG), cerebrosides (CB), and mono- and digalactosyl diacylglycerols. Phosphatidylcholine (PC) > P-ethanolamine (PE) > P-irositol (PI) were the major PL. The fatty acids of PC and PE were quite similar, whereas those of PI were more saturated. CB included only 2-hydroxy fatty acids. Among the steryl lipids, free sterols > SG > ASG, with beta-sitosterol >90% of the total sterol in each.


2004 ◽  
Vol 48 (10) ◽  
pp. 3690-3696 ◽  
Author(s):  
Hanan K. Munayyer ◽  
Paul A. Mann ◽  
Andrew S. Chau ◽  
Taisa Yarosh-Tomaine ◽  
Jonathan R. Greene ◽  
...  

ABSTRACT Posaconazole (POS; SCH 56592) is a novel triazole that is active against a wide variety of fungi, including fluconazole-resistant Candida albicans isolates and fungi that are inherently less susceptible to approved azoles, such as Candida glabrata. In this study, we compared the effects of POS, itraconazole (ITZ), fluconazole (FLZ), and voriconazole (VOR) on sterol biosynthesis in strains of C. albicans (both azole-sensitive and azole-resistant strains), C. glabrata, Aspergillus fumigatus, and Aspergillus flavus. Following exposure to azoles, nonsaponifiable sterols were extracted and resolved by liquid chromatography and sterol identity was confirmed by mass spectroscopy. Ergosterol was the major sterol in all but one of the strains; C. glabrata strain C110 synthesized an unusual sterol in place of ergosterol. Exposure to POS led to a decrease in the total sterol content of all the strains tested. The decrease was accompanied by the accumulation of 14α-methylated sterols, supporting the contention that POS inhibits the cytochrome P450 14α-demethylase enzyme. The degree of sterol inhibition was dependent on both dose and the susceptibility of the strain tested. POS retained activity against C. albicans isolates with mutated forms of the 14α-demethylase that rendered these strains resistant to FLZ, ITZ, and VOR. In addition, POS was a more potent inhibitor of sterol synthesis in A. fumigatus and A. flavus than either ITZ or VOR.


1973 ◽  
Vol 51 (10) ◽  
pp. 1893-1897 ◽  
Author(s):  
Moonja Song ◽  
Neil Tattrie

Total fatty acids of morning glory (Ipomoea sp.) cells grown in suspension cultures for 8 days were determined. Triglycerides, diglycerides, mono- and di-galactosyl-diglycerides were isolated and their constituent fatty acids were analyzed. Sterols and sterol esters as well as the major phospholipids were quantitatively isolated and analyzed at various stages of growth. Palmitic and linolenic acids were the predominant fatty acids in all the isolated compounds until the 5th day of growth when the linolenic acid rapidly decreased and the oleic acid increased until the end of the growth period. Stearic acid remained at about 5% during the entire growth period. Linoleic acid increased from 12 to 20% between 6 and 30 h, then decreased to the original value of the inoculum. The free sterols, β-sitosterol, stigmasterol, and campesterol (72:18:10) changed very little during the 8-day growth period. The three main phospholipids (phosphatidyl-choline, phosphatidyl-ethanolamine, and phosphatidyl-glycerol) increased rapidly between 12 and 48 h of growth but changed very little during the next 6 days.


2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
Author(s):  
Manzoor Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Parveez Gull ◽  
Ovas Ahmad Dar ◽  
Mohmmad Younus Wani ◽  
...  

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.


2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.


2015 ◽  
Vol 7 (4-6) ◽  
pp. 252-263 ◽  
Author(s):  
Kelei Li ◽  
Tao Huang ◽  
Ju-Sheng Zheng ◽  
Jianqin Sun ◽  
Yanqiu Chen ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document