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
Volume1838
Pagination465–473
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
Abstract

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
DOI10.1016/j.bbamem.2013.10.015