Title
Physical Determinants of Amyloid Assembly in Biofilm Formation
Author
Maria Andreasen, Georg Meisl, Jonathan D. Taylor, Thomas C. T. Michaels, Aviad Levin, Daniel E. Otzen, Matthew R. Chapman, Christopher M. Dobson, Steve J. Matthews, Tuomas P. J. Knowles
Year
2019
Journal
mBio
Abstract
A wide range of bacterial pathogens have been shown to form biofilms, which significantly increase their resistance to environmental stresses, such as antibiotics, and are thus of central importance in the context of bacterial diseases. One of the major structural components of these bacterial biofilms are amyloid fibrils, yet the mechanism of fibril assembly and its importance for biofilm formation are currently not fully understood. By studying fibril formation in vitro, in a model system of two common but unrelated biofilm-forming proteins, FapC from Pseudomonas fluorescens and CsgA from Escherichia coli, we found that the two proteins have a common aggregation mechanism. In both systems, fibril formation proceeds via nucleated growth of linear fibrils exhibiting similar measured rates of elongation, with negligible fibril self-replication. These similarities between two unrelated systems suggest that convergent evolution plays a key role in tuning the assembly kinetics of functional amyloid fibrils and indicates that only a narrow window of mechanisms and assembly rates allows for successful biofilm formation. Thus, the amyloid assembly reaction is likely to represent a means for controlling biofilm formation, both by the organism and by possible inhibitory drugs.
Full Article
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Chemical stability, Aggregation, Biochemistry