Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation.

Autor: Sønderby TV; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; Sino-Danish Center (SDC), Eastern Yanqihu Campus, University of Chinese Academy of Sciences, 380 Huaibeizhuang, Huairou District, Beijing, China. Electronic address: https://twitter.com/@tvs1212., Louros NN; Switch Laboratory, VIB-KU Leuven Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: https://twitter.com/LourosNikos., Khodaparast L; Switch Laboratory, VIB-KU Leuven Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: https://twitter.com/@LadanKhodapara1., Khodaparast L; Switch Laboratory, VIB-KU Leuven Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: https://twitter.com/@LalehKhodapara1., Madsen DJ; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark., Olsen WP; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark; Sino-Danish Center (SDC), Eastern Yanqihu Campus, University of Chinese Academy of Sciences, 380 Huaibeizhuang, Huairou District, Beijing, China., Moonen N; Switch Laboratory, VIB-KU Leuven Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium., Nagaraj M; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark., Sereikaite V; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen Ø, Denmark. Electronic address: https://twitter.com/@vitasereikaite., Strømgaard K; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen Ø, Denmark. Electronic address: https://twitter.com/@stromgaardlab., Rousseau F; Switch Laboratory, VIB-KU Leuven Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: https://twitter.com/@stromgaardlab., Schymkowitz J; Switch Laboratory, VIB-KU Leuven Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: https://twitter.com/@stromgaardlab., Otzen DE; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark. Electronic address: dao@inano.au.dk.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2023 Jun 01; Vol. 435 (11), pp. 168039. Date of Electronic Publication: 2023 Jun 16.
DOI: 10.1016/j.jmb.2023.168039
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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