Effects of azole treatments on the physical properties of Candida albicans plasma membrane: A spin probe EPR study

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• 作者：Cristina Sgherri ; Amalia Porta ; Sabrina Castellano ; Calogero Pinzino ; Mike F. Quartacci ; Lucia Calucci
• 关键词：5-DSA ; 5-doxylstearic acid ; 16-DSA ; 16-doxylstearic acid ; CPA18 ; 1-(1-(biphenyl-4-yl)-3-(4-fluorophenyl)propan-2-yl)-1H-imidazole ; CPA109 ; 1-(1-(biphenyl-4-yl)-3-(5-chlorothiophen-2-yl)propan-2-yl)-1H-imidazole ; FLC ; fluconazole ; EPR ; Electron Paramagnetic Resonance ; MOMD ; microscopically ordered macroscopically disordered ; PL ; phospholipid ; PE ; phosphatidylethanolamine ; PS ; phosphatidylserine ; PI ; phosphatidylinositol ; PG ; phosphatidylglycerol ; PA ; phosphatidic acid ; FS ; free sterols
• 刊名：Biochimica et Biophysica Acta (BBA)/Biomembranes
• 出版年：January, 2014
• 年：2014
• 卷：1838
• 期：1
• 页码：465-473
• 全文大小：910 K

文摘

EPR spectroscopy was applied to investigate the effects of the treatment of Candida albicans cells with fluconazole (FLC) and two newly synthesized azoles (CPA18 and CPA109), in a concentration not altering yeast morphology, on the lipid organization and dynamics of the plasma membrane. Measurements were performed in the temperature range between 0 掳C and 40 掳C using 5-doxyl- (5-DSA) and 16-doxyl- (16-DSA) stearic acids as spin probes. 5-DSA spectra were typical of lipids in a highly ordered environment, whereas 16-DSA spectra consisted of two comparable components, one corresponding to a fluid bulk lipid domain in the membrane and the other to highly ordered and motionally restricted lipids interacting with integral membrane proteins. A line shape analysis allowed the relative proportion and the orientational order and dynamic parameters of the spin probes in the different environments to be determined. Smaller order parameters, corresponding to a looser lipid packing, were found for the treated samples with respect to the control one in the region close to the membrane surface probed by 5-DSA. On the other hand, data on 16-DSA indicated that azole treatments hamper the formation of ordered lipid domains hosting integral proteins and/or lead to a decrease in integral protein content in the membrane. The observed effects are mainly ascribable to the inhibition of ergosterol biosynthesis by the antifungal agents, although a direct interaction of the CPA compounds with the membrane bilayer in the region close to the lipid polar head groups cannot be excluded.