Institution: | 1. Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark;2. Sino-Danish Center (SDC), Eastern Yanqihu Campus, University of Chinese Academy of Sciences, 380 Huaibeizhuang, Huairou District, Beijing, China;3. Switch Laboratory, VIB-KU Leuven Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium;4. Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;5. Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen Ø, Denmark |
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. |