1. Modulation of curli assembly and pellicle biofilm formation by chemical and protein chaperones
- Author
-
Erik Chorell, Anders E. G. Lindgren, Pernilla Wittung-Stafshede, Fredrik Almqvist, Matthew George Chapman, Christoffer Bengtsson, Magnus Sellstedt, Margery L. Evans, David A. Hufnagel, Moumita Bhattacharya, Peter M. Tessier, and Emma Andersson
- Subjects
Amyloid ,Pyridones ,Protein subunit ,Clinical Biochemistry ,medicine.disease_cause ,Biochemistry ,Protein Structure, Secondary ,Article ,Small Molecule Libraries ,03 medical and health sciences ,Structure-Activity Relationship ,0302 clinical medicine ,Protein structure ,Drug Discovery ,mental disorders ,medicine ,Curli assembly ,Escherichia coli ,Molecular Biology ,030304 developmental biology ,Pharmacology ,0303 health sciences ,biology ,Escherichia coli Proteins ,Biofilm ,Membrane Transport Proteins ,General Medicine ,Cell biology ,Kinetics ,Chaperone (protein) ,Biofilms ,Drug Design ,biology.protein ,Molecular Medicine ,Chemical chaperone ,Protein Multimerization ,030217 neurology & neurosurgery ,Molecular Chaperones - Abstract
SummaryEnteric 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.”
- Published
- 2013