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

TitleEffects of azole treatments on the physical properties of Candida albicans plasma membrane: a spin probe EPR study.
Publication TypeJournal Article
Year of Publication2014
AuthorsSgherri, C, Porta, A, Castellano, S, Pinzino, C, Quartacci, MF, Calucci, L
JournalBiochimica et biophysica acta
Date Publishedjan
KeywordsAntifungal Agents, Antifungal Agents: chemical synthesis, Antifungal Agents: chemistry, Antifungal Agents: pharmacology, Azoles, Azoles: chemical synthesis, Azoles: chemistry, Azoles: pharmacology, Candida albicans, Candida albicans: chemistry, Cell Fractionation, Cell Membrane, Cell Membrane: chemistry, Cell Membrane: drug effects, Cyclic N-Oxides, Electron spin resonance spectroscopy, Fluconazole, Fluconazole: chemistry, Fluconazole: pharmacology, Membrane Fluidity, Membrane Fluidity: drug effects, Membrane Lipids, Membrane Lipids: chemistry, Membrane Proteins, Membrane Proteins: chemistry, Spin Labels, Temperature

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°C and 40°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.

URLhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84888185652&partnerID=40&md5=abfbf4b52a9f5c3dfbde924352d19eb1 http://www.ncbi.nlm.nih.gov/pubmed/24184423