Plant polyphenols inhibit functional amyloid and biofilm formation in Pseudomonas strains by directing monomers to off-pathway oligomers

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Plant polyphenols inhibit functional amyloid and biofilm formation in Pseudomonas strains by directing monomers to off-pathway oligomers. / Najarzadeh, Zahra; Mohammad-Beigi, Hossein; Pedersen, Jannik Nedergaard; Christiansen, Gunna; Sønderby, Thorbjørn Vincent; Shojaosadati, Seyed Abbas; Morshedi, Dina; Strømgaard, Kristian; Meisl, Georg; Sutherland, Duncan; Pedersen, Jan Skov; Otzen, Daniel.

I: Biomolecules, Bind 9, Nr. 11, 659, 01.11.2019.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

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@article{8eb2b8f91035426da6d0711bf92949cb,
title = "Plant polyphenols inhibit functional amyloid and biofilm formation in Pseudomonas strains by directing monomers to off-pathway oligomers",
abstract = "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.",
keywords = "Aggregation inhibitor, Bacterial amyloid, Extracellular matrix, FapC protein, Peptide array",
author = "Zahra Najarzadeh and Hossein Mohammad-Beigi and Pedersen, {Jannik Nedergaard} and Gunna Christiansen and S{\o}nderby, {Thorbj{\o}rn Vincent} and Shojaosadati, {Seyed Abbas} and Dina Morshedi and Kristian Str{\o}mgaard and Georg Meisl and Duncan Sutherland and Pedersen, {Jan Skov} and Daniel Otzen",
year = "2019",
month = "11",
day = "1",
doi = "10.3390/biom9110659",
language = "English",
volume = "9",
journal = "Biomolecules",
issn = "2218-273X",
number = "11",

}

RIS

TY - JOUR

T1 - Plant polyphenols inhibit functional amyloid and biofilm formation in Pseudomonas strains by directing monomers to off-pathway oligomers

AU - Najarzadeh, Zahra

AU - Mohammad-Beigi, Hossein

AU - Pedersen, Jannik Nedergaard

AU - Christiansen, Gunna

AU - Sønderby, Thorbjørn Vincent

AU - Shojaosadati, Seyed Abbas

AU - Morshedi, Dina

AU - Strømgaard, Kristian

AU - Meisl, Georg

AU - Sutherland, Duncan

AU - Pedersen, Jan Skov

AU - Otzen, Daniel

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

KW - Aggregation inhibitor

KW - Bacterial amyloid

KW - Extracellular matrix

KW - FapC protein

KW - Peptide array

UR - http://www.scopus.com/inward/record.url?scp=85074457349&partnerID=8YFLogxK

U2 - 10.3390/biom9110659

DO - 10.3390/biom9110659

M3 - Journal article

C2 - 31717821

AN - SCOPUS:85074457349

VL - 9

JO - Biomolecules

JF - Biomolecules

SN - 2218-273X

IS - 11

M1 - 659

ER -