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Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers
Self-assembly of proteins to β-sheet rich amyloid fibrils is commonly observed in various neurodegenerative diseases. However, amyloid also occurs in the extracellular matrix of bacterial biofilm, which protects bacteria from environmental stress and antibiotics. Many Pseudomonas strains produce fun...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920965/ https://www.ncbi.nlm.nih.gov/pubmed/31717821 http://dx.doi.org/10.3390/biom9110659 |
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author | Najarzadeh, Zahra Mohammad-Beigi, Hossein Nedergaard Pedersen, Jannik Christiansen, Gunna Sønderby, Thorbjørn Vincent Shojaosadati, Seyed Abbas Morshedi, Dina Strømgaard, Kristian Meisl, Georg Sutherland, Duncan Skov Pedersen, Jan Otzen, Daniel E. |
author_facet | Najarzadeh, Zahra Mohammad-Beigi, Hossein Nedergaard Pedersen, Jannik Christiansen, Gunna Sønderby, Thorbjørn Vincent Shojaosadati, Seyed Abbas Morshedi, Dina Strømgaard, Kristian Meisl, Georg Sutherland, Duncan Skov Pedersen, Jan Otzen, Daniel E. |
author_sort | Najarzadeh, Zahra |
collection | PubMed |
description | Self-assembly of proteins to β-sheet rich amyloid fibrils is commonly observed in various neurodegenerative diseases. However, amyloid also occurs in the extracellular matrix of bacterial biofilm, which protects bacteria from environmental stress and antibiotics. Many Pseudomonas strains produce functional amyloid where the main component is the highly fibrillation-prone protein FapC. FapC fibrillation may be inhibited by small molecules such as plant polyphenols, which are already known to inhibit formation of pathogenic amyloid, but the mechanism and biological impact of inhibition is unclear. Here, we elucidate how polyphenols modify the self-assembly of functional amyloid, with particular focus on epigallocatechin gallate (EGCG), penta-O-galloyl-β-d-glucose (PGG), baicalein, oleuropein, and procyanidin B2. We find EGCG and PGG to be the best inhibitors. These compounds inhibit amyloid formation by redirecting the aggregation of FapC monomers into oligomeric species, which according to small-angle X-ray scattering (SAXS) measurements organize into core-shell complexes of short axis diameters 25–26 nm consisting of ~7 monomers. Using peptide arrays, we identify EGCG-binding sites in FapC’s linker regions, C and N-terminal parts, and high amyloidogenic sequences located in the R2 and R3 repeats. We correlate our biophysical observations to biological impact by demonstrating that the extent of amyloid inhibition by the different inhibitors correlated with their ability to reduce biofilm, highlighting the potential of anti-amyloid polyphenols as therapeutic agents against biofilm infections. |
format | Online Article Text |
id | pubmed-6920965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69209652019-12-24 Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers Najarzadeh, Zahra Mohammad-Beigi, Hossein Nedergaard Pedersen, Jannik Christiansen, Gunna Sønderby, Thorbjørn Vincent Shojaosadati, Seyed Abbas Morshedi, Dina Strømgaard, Kristian Meisl, Georg Sutherland, Duncan Skov Pedersen, Jan Otzen, Daniel E. Biomolecules Article Self-assembly of proteins to β-sheet rich amyloid fibrils is commonly observed in various neurodegenerative diseases. However, amyloid also occurs in the extracellular matrix of bacterial biofilm, which protects bacteria from environmental stress and antibiotics. Many Pseudomonas strains produce functional amyloid where the main component is the highly fibrillation-prone protein FapC. FapC fibrillation may be inhibited by small molecules such as plant polyphenols, which are already known to inhibit formation of pathogenic amyloid, but the mechanism and biological impact of inhibition is unclear. Here, we elucidate how polyphenols modify the self-assembly of functional amyloid, with particular focus on epigallocatechin gallate (EGCG), penta-O-galloyl-β-d-glucose (PGG), baicalein, oleuropein, and procyanidin B2. We find EGCG and PGG to be the best inhibitors. These compounds inhibit amyloid formation by redirecting the aggregation of FapC monomers into oligomeric species, which according to small-angle X-ray scattering (SAXS) measurements organize into core-shell complexes of short axis diameters 25–26 nm consisting of ~7 monomers. Using peptide arrays, we identify EGCG-binding sites in FapC’s linker regions, C and N-terminal parts, and high amyloidogenic sequences located in the R2 and R3 repeats. We correlate our biophysical observations to biological impact by demonstrating that the extent of amyloid inhibition by the different inhibitors correlated with their ability to reduce biofilm, highlighting the potential of anti-amyloid polyphenols as therapeutic agents against biofilm infections. MDPI 2019-10-26 /pmc/articles/PMC6920965/ /pubmed/31717821 http://dx.doi.org/10.3390/biom9110659 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Najarzadeh, Zahra Mohammad-Beigi, Hossein Nedergaard Pedersen, Jannik Christiansen, Gunna Sønderby, Thorbjørn Vincent Shojaosadati, Seyed Abbas Morshedi, Dina Strømgaard, Kristian Meisl, Georg Sutherland, Duncan Skov Pedersen, Jan Otzen, Daniel E. Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers |
title | Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers |
title_full | Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers |
title_fullStr | Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers |
title_full_unstemmed | Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers |
title_short | Plant Polyphenols Inhibit Functional Amyloid and Biofilm Formation in Pseudomonas Strains by Directing Monomers to Off-Pathway Oligomers |
title_sort | plant polyphenols inhibit functional amyloid and biofilm formation in pseudomonas strains by directing monomers to off-pathway oligomers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920965/ https://www.ncbi.nlm.nih.gov/pubmed/31717821 http://dx.doi.org/10.3390/biom9110659 |
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