Pritchard M F, Jack A A, Powell L C, Sadh H, Rye P D, Hill K E, Thomas D W
Advanced Therapies Group, Cardiff University School of Dentistry, College of Biomedical and Life Sciences, Cardiff, UK.
AlgiPharma AS, Sandvika, Norway.
J Appl Microbiol. 2017 Sep;123(3):625-636. doi: 10.1111/jam.13516. Epub 2017 Aug 1.
A novel alginate oligomer (OligoG CF-5/20) has been shown to potentiate antifungal therapy against a range of fungal pathogens. The current study assessed the effect of this oligomer on in vitro virulence factor expression and epithelial invasion by Candida species.
Plate substrate assays and epithelial models were used to assess Candida albicans (CCUG 39343 and ATCC 90028) invasion, in conjunction with confocal laser scanning microscopy and histochemistry. Expression of candidal virulence factors was determined biochemically and by quantitative PCR (qPCR). Changes in surface charge of C. albicans following OligoG treatment were analysed using electrophoretic light scattering. OligoG induced marked alterations in hyphal formation in the substrate assays and reduced invasion in the epithelial model (P < 0·001). Significant dose-dependent inhibition of phospholipase activity in C. albicans was evident following OligoG treatment (P < 0·05). While OligoG binding failed to affect alterations in surface charge (P > 0·05), qPCR demonstrated a reduction in phospholipase B (PLB2) and SAPs (SAP4 and SAP6) expression.
OligoG CF-5/20 reduced in vitro virulence factor expression and invasion by C. albicans.
These results, and the previously described potentiation of antifungal activity, define a potential therapeutic opportunity in the treatment of invasive candidal infections.
一种新型藻酸盐低聚物(OligoG CF - 5/20)已被证明可增强针对多种真菌病原体的抗真菌治疗效果。本研究评估了该低聚物对念珠菌属体外毒力因子表达和上皮侵袭的影响。
采用平板底物试验和上皮模型评估白色念珠菌(CCUG 39343和ATCC 90028)的侵袭情况,并结合共聚焦激光扫描显微镜和组织化学方法。通过生化分析和定量PCR(qPCR)测定念珠菌毒力因子的表达。使用电泳光散射分析OligoG处理后白色念珠菌表面电荷的变化。在底物试验中,OligoG诱导菌丝形成发生显著改变,并减少了上皮模型中的侵袭(P < 0·001)。OligoG处理后,白色念珠菌的磷脂酶活性出现明显的剂量依赖性抑制(P < 0·05)。虽然OligoG结合未影响表面电荷的改变(P > 0·05),但qPCR显示磷脂酶B(PLB2)和天冬氨酸蛋白酶(SAP4和SAP6)的表达降低。
OligoG CF - 5/20降低了白色念珠菌的体外毒力因子表达和侵袭能力。
这些结果,以及先前描述的抗真菌活性增强作用,确定了在治疗侵袭性念珠菌感染方面的潜在治疗机会。