Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea.
AmtixBio Co., Ltd., Hanam, 12925, Republic of Korea.
J Microbiol. 2022 Apr;60(4):438-443. doi: 10.1007/s12275-022-2016-0. Epub 2022 Mar 14.
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.
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。
