Nordihydroguaiaretic Acid (NDGA) Inhibits CsgA Polymerization, Bacterial Amyloid Biogenesis, and Biofilm Formation

Escherichia coli and 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 foodborne illness. As amyloid, curli production 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 in E. coli. NDGA prevents CsgA polymerization in vitro in a dose-dependent manner. NDGA selectively inhibits cellassociated curli assembly in E. coli and inhibits biofilm formation among uropathogenic E. coli in a curli-specific manner. More broadly, our work emphasizes the ability to evaluate and identify bioactive amyloid assembly inhibitors using the powerful gene-directed amyloid biogenesis machinery in E. coli.