Aarhus University Seal

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Thorbjørn V Sønderby, Sino-Danish Centre for Education and Research
  • ,
  • Nikolaos N Louros, KU Leuven
  • ,
  • Ladan Khodaparast, Vlaams Instituut voor Biotechnologie (VIB)
  • ,
  • Laleh Khodaparast, KU Leuven
  • ,
  • Daniel J Madsen
  • ,
  • William P Olsen, Aarhus Univ, Aarhus University, Sect Biostat, Dept Publ Hlth, Sino-Danish Centre for Education and Research
  • ,
  • Nele Moonen, KU Leuven
  • ,
  • Madhu Nagaraj
  • ,
  • Vita Sereikaite, University of Copenhagen
  • ,
  • Kristian Strømgaard, University of Copenhagen
  • ,
  • Frederic Rousseau, KU Leuven
  • ,
  • Joost Schymkowitz, KU Leuven
  • ,
  • Daniel E Otzen

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.

Original languageEnglish
Article number168039
JournalJournal of Molecular Biology
Pages (from-to)168039
Publication statusPublished - 1 Jun 2023

Bibliographical note

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

    Research areas

  • amyloid inhibition, biofilm, functional bacterial amyloid, modulation, peptides

See relations at Aarhus University Citationformats

ID: 326217268