Modulating the Antifungal Activity of Antimycotic Drugs with Farnesol

Introduction. Clinical strains of microorganisms, including opportunistic yeast-like fungi (YLF) of the genus Candida, are resistant to currently used antifungal drugs. In this regard, the search for alternative ways to potentiate the activity of antimicrobial agents in relation to the infectious agent is an important and relevant area of research. The study of combinations of existing antimycotic drugs and a medicinal extract of plant origin – farnesol – is one of the promising approaches in the fight against resistant strains of YLF genus Candida. In our previous studies, farnesol has been shown to exhibit relative activity against YLF Candida albicans biofilms. In this study, we used 6 clinical isolates and one museum strain YLF C. albicans to study the effect of farnesol on the antifungal activity of antimycotic drugs.Aim. To prove that farnesol can increase the antifungal activity of certain antimycotics.Materials and methods. To determine the sensitivity of 7 strains of YLF C. albicans to the antimycotic drugs "Nystatin" (NYS 50 µg), "Ketoconazole" (KET 10 µg), "Clotrimazole" (CTR 10 µg), "Amphotericin B" (AMB 10 µg), "Voriconazole" (VRC 10 µg) disk diffusion test was used. A solution of farnesol in concentrations of 100, 50 and 25 µM in a volume of 25 µl was applied to the disk with the antimycotic drug. Sterile physiological (PhS) solution was used as a control (pH 7.0; V = 25 µl).Results and discussion. In 34.3 % of of experiments we can talk about the modulating effect of farnesol solutions on the antifungal activity of antimycotic drugs. In all these cases, the sensitivity of YLF C. albicans to the antimycotic drug increases.Conclusion. The results of this study provide useful information for understanding the mechanism of QS-molecules action with antifungal activity, as well as they are the basis for the practical application of some QS-molecules in the treatment of infectious diseases caused by YLF of the genus Candida. The study demonstrates that farnesol can be recommended as an active substance that improves the sensitivity of YLF Candida to antimycotic drugs, especially in the case of multi-resistant strains Candida.

Effect of Cold Atmospheric Plasma Jet Associated to Polyene Antifungals on Candida albicans Biofilms

The increasing incidence of antifungal resistance represents a great challenge in the medical area and, for this reason, new therapeutic alternatives for the treatment of fungal infections are urgently required. Cold atmospheric plasma (CAP) has been proposed as a promising alternative technique for the treatment of superficial candidiasis, with inhibitory effect both in vitro and in vivo. However, little is known on the association of CAP with conventional antifungals. The aim of this study was to evaluate the effects of the association between CAP and conventional polyene antifungals on Candida albicans biofilms. C. albicans SC 5314 and a clinical isolate were used to grow 24 or 48 h biofilms, under standardized conditions. After that, the biofilms were exposed to nystatin, amphotericin B and CAP, separately or in combination. Different concentrations of the antifungals and sequences of treatment were evaluated to establish the most effective protocol. Biofilms viability after the treatments was compared to negative control. Data were compared by One-way ANOVA and post hoc Tukey (5%). The results demonstrate that 5 min exposure to CAP showed more effective antifungal effect on biofilms when compared to nystatin and amphotericin B. Additionally, it was detected that CAP showed similar (but smaller in magnitude) effects when applied in association with nystatin and amphotericin B at 40 µg/mL and 60 µg/mL. Therefore, it can be concluded that the application of CAP alone was more effective against C. albicans biofilms than in combination with conventional polyene antifungal agents.

Lichen Polyphenolic Compounds for the Eradication of Candida albicans Biofilms

Lichens, due to their symbiotic nature (association between fungi and algae), constitute a chemical factory of original compounds. Polyphenolic compounds (depsides and depsidones) are the main constituents of lichens and are exclusively biosynthesized by these organisms. A panel of 11 polyphenols was evaluated for their anti-biofilm activity against Candida albicans biofilms on the maturation phase (anti-maturation) (MMIC50) as well as on preformed 24-h-old biofilm (anti-biofilm) (MBIC50) using the XTT assay. Minimum inhibitory concentrations of compounds (MICs) against C. albicans planktonic yeast were also determined using a broth microdilution method. While none of the tested compounds were active against planktonic cells (IC50 > 100 µg/ml), three depsides slowed the biofilm maturation (MMIC50 ≤12.5 µg/ml after 48 h of contact with Candida cells). Evernic acid was able to both slow the maturation and reduce the already formed biofilms with MBIC50 ≤12.5 µg/ml after 48 h of contact with the biofilm. This compound shows a weak toxicity against HeLa cells (22%) at the minimal active concentration and no hemolytic activity at 100 µg/ml. Microscopic observations of evernic acid and optimization of its solubility were performed to further study this compound. This work confirmed the anti-biofilm potential of depsides, especially evernic acid, and allows to establish the structure–activity relationships to better explain the anti-biofilm potential of these compounds.

Plasma Treatment Effects on Oral Candida albicans Biofilms

The objective of this study is to evaluate the plasma treatment effects on oral fungal biofilms. Candida albicans biofilms were developed on the 48-well plate to serve as a model of oral fungal biofilm. The treatment of 0.2% chlorhexidine digluconate (CHX) was used as a positive control compared with plasma treatments. The efficacy of treatments was determined by 3-(4,5-dimethylazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and confocal laser scanning microscope (CLSM). The survival percentage of Candida albicans decreased from 52% to 27% as the plasma power increased from 6mA to 8mA and plasma exposure time extended from 2 min to 10 min. Moreover, it was found that there is a synergistic effect of the combination of plasma and CHX treatments. Scanning electron microscopy (SEM) examination indicated severe cell damages resulting from plasma treatment. In conclusion, the low-temperature plasma treatment is effective in deactivating Candida albicans biofilms and thus provides a promising alternative to disinfect oral fungal biofilms.

Development of a Solid Dispersion of Nystatin with Maltodextrin as a Carrier Agent: Improvements in Antifungal Efficacy against Candida spp. Biofilm Infections

The aim of this study was to improve the treatment of Candida albicans biofilms through the use of nystatin solid dispersions developed using maltodextrins as a hyperosmotic carrier. Characterization studies by differential scanning calorimetry, X-ray diffraction, dissolution studies, and particle size analysis were performed to evaluate changes in nystatin crystallinity. Antifungal activity and anti-biofilm efficacy were assessed by microbiological techniques. The results for nystatin solid dispersions showed that the enhancement of antifungal activity may be related to the high proportions of maltodextrins. Anti-biofilm assays showed a significant reduction (more than 80%) on biofilm formation with SD-N:MD [1:6] compared to the nystatin reference suspension. The elaboration process and physicochemical properties of SD-N:MD [1:6] could be a promising strategy for treatment of Candida biofilms.