Modulation of Curli Assembly and Pellicle Biofilm Formation by Chemical and Protein Chaperones

Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces that share structural and biochemical properties with disease-associated amyloids. Here, we test rationally designed 2-pyridone compounds for their ability to alter amyloid formation of the major curli subunit CsgA. We identified several compounds that discourage CsgA amyloid formation and several compounds that accelerate CsgA amyloid formation. The ability of inhibitor compounds to stop growing CsgA fibers was compared to the same property of the CsgA chaperone, CsgE. CsgE blocked CsgA amyloid assembly and arrested polymerization when added to actively polymerizing fibers. Additionally, CsgE and the 2-pyridone inhibitors prevented biofilm formation by Escherichia coli at the air-liquid interface of a static culture. We demonstrate that curli amyloid assembly and curli-dependent biofilm formation can be modulated not only by protein chaperones, but also by “chemical chaperones.” •2-Pyridone derivatives were identified that accelerate CsgA amyloid formation•Rationally designed 2-pyridones improve amyloid-inhibitory activity•Antibody fragments designed to specifically detect CsgA amyloid•CsgE prevents pellicle biofilm formation and arrests active CsgA polymerization Amyloids are the hallmark of many neurodegenerative diseases. Interestingly, amyloids also provide structural integrity to bacterial biofilms. Andersson et al. report several compounds that act as modulators of amyloid formation, with both antiamyloid and proamyloid characteristics.