Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation
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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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 168039 |
| Tidsskrift | Journal of Molecular Biology |
| Vol/bind | 435 |
| Udgave nummer | 11 |
| ISSN | 0022-2836 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
T.V.S. M.N. and D.E.O. gratefully acknowledge support from the Independent Research Foundation Denmark | Natural Sciences (grant no. 8021-00208B). T.V.S. and W.P.O. are grateful for support from the Sino-Danish Center. The Switch Laboratory was supported by the Flanders Institute for Biotechnology (VIB, grant no. C0401 to FR and JS), KU Leuven, the Fund for Scientific Research Flanders (FWO, project grants G0C3522N to FR and G045920N to JS; Postdoctoral Fellowships 12P0919N and 12P0922N to NL, and 1231021 N to Ladan K), and the Stichting Alzheimer Onderzoek / Fondation Recherche Alzheimer (SAO-FRA 2019/0015 & SAO-FRA 2022/0030 to FR, SAO-FRA 2020/0009 to JS, and SAO-FRA 2020/0013 & SAO-FRA 2022/0020 to NL). We thank the VIB BioImaging Core for training, technical support, and access to the instrument park. The Zeiss SIM Elyra microscope was acquired through a CLME grant from Minister Lieten to the VIB BioImaging Core. 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.
Funding Information:
T.V.S., M.N. and D.E.O. gratefully acknowledge support from the Independent Research Foundation Denmark | Natural Sciences (grant no. 8021-00208B). T.V.S. and W.P.O. are grateful for support from the Sino-Danish Center. The Switch Laboratory was supported by the Flanders Institute for Biotechnology (VIB, grant no. C0401 to FR and JS), KU Leuven, the Fund for Scientific Research Flanders (FWO, project grants G0C3522N to FR and G045920N to JS; Postdoctoral Fellowships 12P0919N and 12P0922N to NL, and 1231021 N to Ladan K), and the Stichting Alzheimer Onderzoek / Fondation Recherche Alzheimer (SAO‐FRA 2019/0015 & SAO-FRA 2022/0030 to FR, SAO‐FRA 2020/0009 to JS, and SAO-FRA 2020/0013 & SAO-FRA 2022/0020 to NL). We thank the VIB BioImaging Core for training, technical support, and access to the instrument park. The Zeiss SIM Elyra microscope was acquired through a CLME grant from Minister Lieten to the VIB BioImaging Core.
Publisher Copyright:
© 2023 The Authors
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