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11g, a Potent Antifungal Candidate, Enhances Candida albicans Immunogenicity by Unmasking β-Glucan in Fungal Cell Wall.
Frontiers in Microbiology ( IF 4.0 ) Pub Date : 2020-05-25 , DOI: 10.3389/fmicb.2020.01324
Xin Huang 1 , Yu Liu 2 , Tingjunhong Ni 1 , Liping Li 1 , Lan Yan 2 , Maomao An 1 , Dazhi Zhang 2 , Yuanying Jiang 1, 2
Affiliation  

In the course of optimizing GPI biosynthesis inhibitors, we designed and synthetized a 2-aminonicotinamide derivative named 11g. After evaluating the antifungal activity of compound 11g in vitro, we investigated the influences of 11g on fungi immunogenicity. In addition, we also took advantage of murine systemic candidiasis model to investigate the protective effects of 11g in vivo. Results show that 11g exhibited potent antifungal activity both in vitro and in vivo. Further study shows that 11g caused the unmasking of fungi β-glucan layer, leading to stronger immune responses in macrophages through Dectin-1. These results suggest that 11g is a very promising antifungal candidate, which assists in eliciting stronger immune responses to help host immune system disposing pathogens. The discovery of 11g might expand the toolbox of fungal infection treatment.



中文翻译:

强大的抗真菌候选物质11g通过揭露真菌细胞壁中的β-葡聚糖,增强了白色念珠菌的免疫原性。

在优化GPI生物合成抑制剂的过程中,我们设计并合成了一种名为11g的2-氨基烟酰胺衍生物。评价化合物11g的抗真菌活性后体外,我们调查了11g对真菌免疫原性的影响。此外,我们还利用小鼠系统性念珠菌病模型研究了11g的保护作用体内。结果显示11g均显示出有效的抗真菌活性体外体内。进一步的研究表明,11g引起真菌β-葡聚糖层的暴露,从而导致通过Dectin-1的巨噬细胞产生更强的免疫反应。这些结果表明11g是非常有前途的抗真菌候选物,其有助于引起更强的免疫应答,以帮助宿主免疫系统处置病原体。11g的发现可能会扩大真菌感染治疗的工具箱。

更新日期:2020-06-30
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