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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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