Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, Changchun City, Jilin Province, 130024 P. R. China.
Division of Clinical Epidemiology, First Hospital of Jilin University, Changchun City, Jilin Province, 130021 P. R. China.
Sci Rep. 2016 Aug 25;6:32256. doi: 10.1038/srep32256.
Candida albicans (C. albicans) is an important human commensal and opportunistic fungal pathogen. Secreted aspartyl proteinases (Saps) are a major virulence trait of C. albicans, and among these proteases Sap2 has the highest expression levels. It is possible that antibodies against Sap2 could provide an antifungal effect. In this study, two phages displaying anti-rSap2 single chain variable fragments (scFvs) were screened from human single fold scFv libraries, and their potential therapeutic roles were evaluated using a murine model infected by C. albicans. The in vivo efficacies were assessed by mortality rates, fungal burden and histological examination. Overall survival rates were significantly increased while the colony counts and infectious foci were significantly decreased after treatment with the scFv-phages relative to the control groups. In order to investigate the immune response provoked by scFv-phages, three kinds of cytokines (Th1, Th2 and Th17 types) were measured and a clear immune response was observed. These findings suggest that anti-rSap2 scFv-phages have potential in the therapy of systemic infection caused by C. albicans.
白色念珠菌(C. albicans)是一种重要的人体共生菌和机会性真菌病原体。分泌的天冬氨酸蛋白酶(Saps)是 C. albicans 的主要毒力特征,其中 Sap2 的表达水平最高。针对 Sap2 的抗体可能具有抗真菌作用。在这项研究中,从人源单结构域 scFv 文库中筛选出了两种展示抗 rSap2 单链可变片段(scFv)的噬菌体,并使用白色念珠菌感染的小鼠模型评估了它们的潜在治疗作用。通过死亡率、真菌负荷和组织学检查评估体内疗效。与对照组相比,用 scFv-噬菌体治疗后,总生存率显著提高,而菌落计数和感染灶显著减少。为了研究 scFv-噬菌体引起的免疫反应,测量了三种细胞因子(Th1、Th2 和 Th17 型),并观察到了明显的免疫反应。这些发现表明,抗 rSap2 scFv-噬菌体在治疗由白色念珠菌引起的全身感染方面具有潜力。