Nordihydroguaiaretic Acid (NDGA) Inhibits CsgA Polymerization, Bacterial Amyloid Biogenesis, and Biofilm Formation
Nordihydroguaiaretic Acid (NDGA) Inhibits CsgA Polymerization, Bacterial Amyloid Biogenesis, and Biofilm Formation
复制标题
去甲二氢愈创木酸 (NDGA) 抑制 CsgA 聚合、细菌淀粉样蛋白生物发生和生物膜形成
DOI：
10.1002/cbic.202300266
复制
发表时间：
2023
期刊：
影响因子：
3.2
通讯作者：
Cegelski, Lynette
中科院分区：
文献类型：
--
作者：
Visser, Joshua A.;Yager, Deborah;Chambers, Schuyler A;Lim, Ji Youn;Cao, Xujun;Cegelski, Lynette
大肠杆菌和其他肠杆菌科细菌通过共同产生卷曲淀粉样纤维和磷酸乙醇胺纤维素而在强健的生物膜群落中茁壮成长。Curli促进粘附到非生物表面以及植物和人类宿主组织，并与尿路感染和食源性疾病的发病机制有关。在宿主中产生卷曲也与神经退行性疾病的发病机制有关。本文报道天然产物去甲二氢愈创木酸（NDGA）是一种有效的杀线虫剂。杆菌NDGA以剂量依赖性方式阻止CsgA体外聚合。 NDGA选择性地抑制细胞相关卷曲组装并抑制尿路致病性E。大肠杆菌生物膜形成。更广泛地说，这项工作强调了通过使用E中强大的基因指导的淀粉样蛋白生物发生机制来评估和鉴定生物活性淀粉样蛋白组装抑制剂的能力。杆菌
Escherichia coliand other Enterobacteriaceae thrive in robust biofilm communities through the coproduction of curli amyloid fibers and phosphoethanolamine cellulose. Curli promote adhesion to abiotic surfaces and plant and human host tissues and are associated with pathogenesis in urinary tract infection and food‐borne illness. The production of curli in the host has also been implicated in the pathogenesis of neurodegenerative diseases. We report that the natural product nordihydroguaiaretic acid (NDGA) is effective as a curlicide inE. coli. NDGA prevents CsgA polymerization in vitro in a dose‐dependent manner. NDGA selectively inhibits cell‐associated curli assembly and inhibits uropathogenicE. colibiofilm formation. More broadly, this work emphasizes the ability to evaluate and identify bioactive amyloid assembly inhibitors by using the powerful gene‐directed amyloid biogenesis machinery inE. coli.