Alginate oligosaccharides enhance the antifungal activity of nystatin against candidal biofilms

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

David W. Thomas¹  Manon F. Pritchard¹  Jennifer Y. M. Adams¹  Katja E. Hill¹  Lydia C. Powell²  Charlène Py³  Anaϊs Oger³  Philip D. Rye⁴  Christopher von Ruhland⁵  Salvatore A. Gazze⁶  Lewis W. Francis⁶  David Owens⁷  Sadik Quoraishi⁸ 

[1] Advanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United Kingdom;Advanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United Kingdom;Microbiology and Infectious Disease group, Swansea University Medical School, Swansea, United Kingdom;Advanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United Kingdom;School of Engineering, University of Angers, Angers, France;AlgiPharma AS, Sandvika, Norway;Central Biotechnology Services, Cardiff University School of Medicine, Cardiff, United Kingdom;Centre for Nanohealth, Swansea University Medical School, Swansea, United Kingdom;Head and Neck Directorate, University Hospital of Wales, Cardiff, United Kingdom;Otolaryngology Department, New Cross Hospital, Wolverhampton, United Kingdom;

关键词: antifungal;    alginate oligosaccharide;    nystatin;    Candida;    biofilm;   

DOI  :  10.3389/fcimb.2023.1122340

 received in 2022-12-12, accepted in 2023-01-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundThe 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.MethodsThe 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).ResultsMIC 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).ConclusionsAntimicrobial 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.

【 授权许可】

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Copyright © 2023 Powell, Adams, Quoraishi, Py, Oger, Gazze, Francis, von Ruhland, Owens, Rye, Hill, Pritchard and Thomas