Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, amyloid inhibition, biofilm, functional bacterial amyloid, modulation, peptides, PROTEIN AGGREGATION, MOLECULAR-MECHANISMS, NUCLEATOR PROTEIN, CURLI, SUBUNIT, OPERONS, SERVER, CSGB, Amyloid, Amyloidogenic Proteins, Bacterial Proteins, Biofilms, Escherichia coli, Escherichia coli Proteins, Peptides, Protein Aggregates, Pseudomonas aeruginosa, Protein Stability, G0C3522N#56762789, G045920N#55524473, 12P0919N#54767906, 12P0922N#56382403, 1231021N#55822149, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 0605 Microbiology, 3101 Biochemistry and cell biology, 3107 Microbiology

Abstract:

Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive amyloid formation. Here, we demonstrate the use of aggregation-modulating peptides to knock down CsgA protein into aggregates with low stability and altered morphology. Remarkably, these CsgA-peptides also modulate fibrillation of the unrelated functional amyloid protein FapC from Pseudomonas, possibly through recognition of FapC segments with structural and sequence similarity with CsgA. The peptides also reduce the level of biofilm formation in E. coli and P. aeruginosa, demonstrating the potential for selective amyloid targeting to combat bacterial biofilm.