Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms

by Selleckchem | Mar 11 2023

Background: The increasing prevalence of invasive fungal infections in immuno-compromised patients is a considerable cause of morbidity and mortality. With the rapid emergence of antifungal resistance and an inadequate pipeline of new therapies, novel treatment strategies are now urgently required.

Methods: The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of Candida spp. (C. albicans, C. glabrata, C. parapsilosis, C. auris, C. tropicalis and C. dubliniensis), in both planktonic and biofilm assays, to determine its potential clinical utility to enhance the treatment of candidal infections. The effect of OligoG (0-6%) ± nystatin on Candida spp. was examined in minimum inhibitory concentration (MIC) and growth curve assays. Antifungal effects of OligoG and nystatin treatment on biofilm formation and disruption were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM) and ATP cellular viability assays. Effects on the cell membrane were determined using permeability assays and transmission electron microscopy (TEM).

Results: MIC and growth curve assays demonstrated the synergistic effects of OligoG (0-6%) with nystatin, resulting in an up to 32-fold reduction in MIC, and a significant reduction in the growth of C. parapsilosis and C. auris (minimum significant difference = 0.2 and 0.12 respectively). CLSM and SEM imaging demonstrated that the combination treatment of OligoG (4%) with nystatin (1 µg/ml) resulted in significant inhibition of candidal biofilm formation on glass and clinical grade silicone surfaces (p < 0.001), with increased cell death (p < 0.0001). The ATP biofilm disruption assay demonstrated a significant reduction in cell viability with OligoG (4%) alone and the combined OligoG/nystatin (MIC value) treatment (p < 0.04) for all Candida strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the Candida cell membrane, with increased permeability when compared to the untreated control (p < 0.001).

Conclusions: Antimicrobial synergy between OligoG and nystatin against Candida spp. highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections, to overcome the inherent tolerance of biofilm structures to antifungal agents.

Comments：

Summary:

This study investigated the potential clinical utility of OligoG, an alginate oligosaccharide, in conjunction with nystatin against Candida spp. The combination treatment was tested against planktonic and biofilm forms of Candida spp. The results demonstrated that the combination of OligoG and nystatin showed synergistic effects, resulting in a significant reduction in MIC and growth of Candida spp. The combination treatment also showed significant inhibition of candidal biofilm formation, increased cell death, and induced structural reorganization of the Candida cell membrane with increased permeability. The study highlights the potential utility of this combination therapy in the prevention and topical treatment of candidal biofilm infections.

Explanation:

Candida spp. is a major cause of invasive fungal infections, especially in immunocompromised patients, and is associated with significant morbidity and mortality. The increasing prevalence of antifungal resistance and an inadequate pipeline of new therapies have led to the urgent need for novel treatment strategies. In this study, the authors investigated the potential clinical utility of OligoG in conjunction with nystatin against Candida spp.

The results of the study demonstrated that the combination treatment of OligoG and nystatin showed synergistic effects, resulting in a significant reduction in MIC and growth of Candida spp. The combination treatment also showed significant inhibition of candidal biofilm formation, increased cell death, and induced structural reorganization of the Candida cell membrane with increased permeability.

The study has several strengths, including the use of multiple assays to evaluate the efficacy of the combination treatment against Candida spp. The study also highlights the potential utility of OligoG in conjunction with nystatin as a novel treatment strategy for candidal biofilm infections.

However, there are some limitations to the study. The study only evaluated the efficacy of the combination treatment against a limited range of Candida spp. The study also did not evaluate the potential toxicity of the combination treatment in vivo. Further studies are needed to evaluate the safety and efficacy of the combination treatment in animal models and in clinical trials.