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新型抗真菌药物 AB-22 显示出体外抗白念珠菌菌丝生长和生物膜形成的活性,并具有治疗系统性念珠菌病的潜力。

The novel antifungal agent AB-22 displays in vitro activity against hyphal growth and biofilm formation in Candida albicans and potency for treating systemic candidiasis.

机构信息

Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.

AmtixBio Co., Ltd., Hanam, 12925, Republic of Korea.

出版信息

J Microbiol. 2022 Apr;60(4):438-443. doi: 10.1007/s12275-022-2016-0. Epub 2022 Mar 14.

Abstract

Systemic candidiasis, which is mainly caused by Candida albicans, is a serious acute fungal infection in the clinical setting. In a previous study, we reported that compound 22h (designated as AB-22 in this study), a vinyl sulfate compound, is a fast-acting fungicidal agent against a broad spectrum of fungal pathogens. In this study, we aimed to further analyze the in vitro and in vivo efficacy of AB-22 against filamentation, biofilm formation, and virulence of C. albicans. Under in vitro hyphal growth-inducing condition, AB-22 effectively inhibited germ tube formation and hyphal growth, which are required for the initiation of biofilm formation. Indeed, AB-22 significantly suppressed C. albicans biofilm formation in a dose-dependent manner. Moreover, AB-22 treatment inhibited the normal induction of ALS3, HWP1, and ECE1, which are all required for hyphal transition in C. albicans. Furthermore, AB-22 treatment increased the survival of mice systemically infected with C. albicans. In conclusion, in addition to its fungicidal activity, AB-22 inhibits filamentation and biofilm formation in C. albicans, which could collectively contribute to its potent in vivo efficacy against systemic candidiasis.

摘要

系统性念珠菌病主要由白念珠菌引起,是临床中一种严重的急性真菌感染。在之前的研究中,我们报道了化合物 22h(在本研究中指定为 AB-22),一种乙烯基硫酸盐化合物,是一种针对广谱真菌病原体的快速杀菌剂。在本研究中,我们旨在进一步分析 AB-22 对白色念珠菌丝状生长、生物膜形成和毒力的体外和体内疗效。在体外菌丝生长诱导条件下,AB-22 有效抑制了芽管形成和菌丝生长,这是生物膜形成的起始所必需的。事实上,AB-22 以剂量依赖性方式显著抑制白色念珠菌生物膜形成。此外,AB-22 处理抑制 ALS3、HWP1 和 ECE1 的正常诱导,这些都是白色念珠菌菌丝过渡所必需的。此外,AB-22 处理增加了系统性感染白色念珠菌的小鼠的存活率。总之,除了杀菌活性外,AB-22 还抑制白色念珠菌的丝状生长和生物膜形成,这可能共同有助于其对系统性念珠菌病的强大体内疗效。

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