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

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.

Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans

“…Several studies are devoted to validate the potency of azoles as inhibitors of 14 α-demethylase [ 5 ]. Impairment of ergosterol biosynthesis by these compounds has also been documented [ 4 , 6 ]. However, prolonged use of some azoles as antifungal agents has resulted in the emergence of drug resistance among certain fungal strains [ 7 – 9 ].…”

Antimicrobial and Antibiofilm Activity of Chitosan on the Oral Pathogen Candida albicans

“…These Candida -derived infections may occur in the skin, mucous membranes (such as the mouth and vagina) and in the viscera, with the main etiological agent being Candida albicans [ 1 , 2 ]. Among the various human fungal pathogens, C. albicans accounts for the majority of systemic infections in immunocompromised patients, with overall mortality rates ranging from 29% to 76% [ 2 , 3 , 4 , 5 , 6 ]. This opportunistic fungi causes great problems, as it is resistant to most antimicrobial compounds, namely amphotericin-B, which is considered the standard for the treatment of systemic mycoses.…”

“…This opportunistic fungi causes great problems, as it is resistant to most antimicrobial compounds, namely amphotericin-B, which is considered the standard for the treatment of systemic mycoses. Despite still being considered the drug of choice against C. albicans , these antifungal agents are being increasingly reported as inefficient with numerous cases of resistances, particularly to fluconazole, being observed [ 1 , 2 , 3 , 4 ]. This problem has led to the search for alternative drugs and compounds to be used in the treatment and management of C. albicans infections.…”

The synthesis, regulation, and functions of sterols inCandida albicans: Well-known but still lots to learn

“…17 In a spin probe electron paramagnetic resonance (EPR) study, Sgherri et al detected that azole treatment disrupted the formation of the ordered lipid bilayer and/or decreased the content of integral membrane proteins. 18 In addition, the membranes of organelles and the fusion of transport vesicles are dependent on the correct assemblies of sterols and other lipids. In this review, we present the synthesis of ergosterol in the opportunistic pathogenic fungus C. albicans and summarize key genetic mutations in ergosterol biosynthesis and transcriptional factors, focusing on their effects on drug sensitivity.…”