Advanced Therapies Group, Cardiff University School of Dentistry, Cardiff, United Kingdom.
Microbiology and Infectious Disease group, Swansea University Medical School, Swansea, United Kingdom.
Front Cell Infect Microbiol. 2023 Jan 31;13:1122340. doi: 10.3389/fcimb.2023.1122340. eCollection 2023.
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.
The antifungal activity of the alginate oligosaccharide OligoG in conjunction with nystatin was tested against a range of spp. (, , , , and ), 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 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).
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 and (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 ( < 0.001), with increased cell death ( < 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 ( < 0.04) for all strains tested. TEM studies revealed the combined OligoG/nystatin treatment induced structural reorganization of the cell membrane, with increased permeability when compared to the untreated control ( < 0.001).
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.
免疫功能低下患者侵袭性真菌感染的发病率不断上升，是发病率和死亡率的重要原因。由于抗真菌耐药性的迅速出现和新疗法的供应不足，现在迫切需要新的治疗策略。
用藻酸盐低聚糖寡糖 OligoG 联合制霉菌素检测一系列念珠菌属物种（、、、、和）的抗真菌活性，在浮游和生物膜测定中，以确定其潜在的临床应用价值，以增强念珠菌感染的治疗效果。在最低抑菌浓度（MIC）和生长曲线测定中，研究了 OligoG（0-6%）±制霉菌素对 spp.的影响。采用共焦激光扫描显微镜（CLSM）、扫描电子显微镜（SEM）和 ATP 细胞活力测定法研究 OligoG 和制霉菌素处理对生物膜形成和破坏的抗真菌作用。用通透性测定和透射电子显微镜（TEM）测定细胞膜的影响。
MIC 和生长曲线测定表明，OligoG（0-6%）与制霉菌素具有协同作用，导致 MIC 降低 32 倍， 和 生长显著减少（最小显著差异分别为 0.2 和 0.12）。CLSM 和 SEM 成像表明，OligoG（4%）联合制霉菌素（1μg/ml）治疗可显著抑制玻璃和临床级硅酮表面念珠菌生物膜的形成（<0.001），细胞死亡增加（<0.0001）。ATP 生物膜破坏试验表明，单独使用 OligoG（4%）和联合使用 OligoG/制霉菌素（MIC 值）治疗时，所有测试菌株的细胞活力均显著降低（<0.04）。TEM 研究表明，与未处理的对照组相比，联合使用 OligoG/制霉菌素治疗诱导了 细胞膜的结构重组，通透性增加（<0.001）。
OligoG 和制霉菌素对念珠菌属的抗菌协同作用突出了这种联合治疗在预防和局部治疗念珠菌生物膜感染方面的潜在应用价值，以克服生物膜结构对抗真菌药物的固有耐受性。
