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Daniel Otzen

Human Fibrinogen Inhibits Amyloid Assembly of Most Phenol-Soluble Modulins from Staphylococcus aureus

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Human Fibrinogen Inhibits Amyloid Assembly of Most Phenol-Soluble Modulins from Staphylococcus aureus. / Najarzadeh, Zahra; Nielsen, Janni; Farzadfard, Azad; Sereikaite, Vita; Strømgaard, Kristian; Meyer, Rikke Louise; Otzen, Daniel Erik.

In: ACS Omega, Vol. 6, No. 34, 08.2021, p. 21960-21970.

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Najarzadeh, Zahra ; Nielsen, Janni ; Farzadfard, Azad ; Sereikaite, Vita ; Strømgaard, Kristian ; Meyer, Rikke Louise ; Otzen, Daniel Erik. / Human Fibrinogen Inhibits Amyloid Assembly of Most Phenol-Soluble Modulins from Staphylococcus aureus. In: ACS Omega. 2021 ; Vol. 6, No. 34. pp. 21960-21970.

Bibtex

@article{05e1ac4743114def956c58ba8d3b3f28,
title = "Human Fibrinogen Inhibits Amyloid Assembly of Most Phenol-Soluble Modulins from Staphylococcus aureus",
abstract = "Functional amyloids are highly organized protein/peptide structures that inter alia promote biofilm formation in different bacteria. One such example is provided by a family of 20-45 residue-long peptides called phenol-soluble modulins (PSMs) from Staphylococcus aureus. External components such as eukaryotic host proteins, which alter self-assembly of bacterial amyloids, can affect the biofilm matrix. Here, we studied the effect of the highly prevalent human plasma protein fibrinogen (Fg) on fibrillation of PSMs. Fg inhibits or suppresses fibrillation of most PSMs tested (PSMα1, PSMβ1, and PSMβ2) except for PSMα3, whose already rapid aggregation is accelerated even further by Fg but leads to amorphous β-rich aggregates rather than fibrils. Fg also induces PSMβ2 to form amorphous aggregates and diverts PSMα1 into off-pathway oligomers which consist of both Fg and PSMα1 and cannot seed fibrillation. Peptide arrays showed that Fg bound to the N-terminus of PSMα1, while it bound to the entire length of PSMα3 (except the C terminus) and to the C-termini of PSMβ1 and PSMβ2. The latter peptides are all positively charged, while Fg is negatively charged at physiological pH. The positive charges complement Fg's net negative charge of -7.6 at pH 7.4. Fg's ability to inhibit PSM fibrillation reveals a potential host-defense mechanism to prevent bacterial biofilm growth and infections in the human body.",
author = "Zahra Najarzadeh and Janni Nielsen and Azad Farzadfard and Vita Sereikaite and Kristian Str{\o}mgaard and Meyer, {Rikke Louise} and Otzen, {Daniel Erik}",
note = "{\textcopyright} 2021 The Authors. Published by American Chemical Society.",
year = "2021",
month = aug,
doi = "10.1021/acsomega.1c02333",
language = "English",
volume = "6",
pages = "21960--21970",
journal = "ACS Omega",
issn = "2470-1343",
publisher = "ACS Publications",
number = "34",

}

RIS

TY - JOUR

T1 - Human Fibrinogen Inhibits Amyloid Assembly of Most Phenol-Soluble Modulins from Staphylococcus aureus

AU - Najarzadeh, Zahra

AU - Nielsen, Janni

AU - Farzadfard, Azad

AU - Sereikaite, Vita

AU - Strømgaard, Kristian

AU - Meyer, Rikke Louise

AU - Otzen, Daniel Erik

N1 - © 2021 The Authors. Published by American Chemical Society.

PY - 2021/8

Y1 - 2021/8

N2 - Functional amyloids are highly organized protein/peptide structures that inter alia promote biofilm formation in different bacteria. One such example is provided by a family of 20-45 residue-long peptides called phenol-soluble modulins (PSMs) from Staphylococcus aureus. External components such as eukaryotic host proteins, which alter self-assembly of bacterial amyloids, can affect the biofilm matrix. Here, we studied the effect of the highly prevalent human plasma protein fibrinogen (Fg) on fibrillation of PSMs. Fg inhibits or suppresses fibrillation of most PSMs tested (PSMα1, PSMβ1, and PSMβ2) except for PSMα3, whose already rapid aggregation is accelerated even further by Fg but leads to amorphous β-rich aggregates rather than fibrils. Fg also induces PSMβ2 to form amorphous aggregates and diverts PSMα1 into off-pathway oligomers which consist of both Fg and PSMα1 and cannot seed fibrillation. Peptide arrays showed that Fg bound to the N-terminus of PSMα1, while it bound to the entire length of PSMα3 (except the C terminus) and to the C-termini of PSMβ1 and PSMβ2. The latter peptides are all positively charged, while Fg is negatively charged at physiological pH. The positive charges complement Fg's net negative charge of -7.6 at pH 7.4. Fg's ability to inhibit PSM fibrillation reveals a potential host-defense mechanism to prevent bacterial biofilm growth and infections in the human body.

AB - Functional amyloids are highly organized protein/peptide structures that inter alia promote biofilm formation in different bacteria. One such example is provided by a family of 20-45 residue-long peptides called phenol-soluble modulins (PSMs) from Staphylococcus aureus. External components such as eukaryotic host proteins, which alter self-assembly of bacterial amyloids, can affect the biofilm matrix. Here, we studied the effect of the highly prevalent human plasma protein fibrinogen (Fg) on fibrillation of PSMs. Fg inhibits or suppresses fibrillation of most PSMs tested (PSMα1, PSMβ1, and PSMβ2) except for PSMα3, whose already rapid aggregation is accelerated even further by Fg but leads to amorphous β-rich aggregates rather than fibrils. Fg also induces PSMβ2 to form amorphous aggregates and diverts PSMα1 into off-pathway oligomers which consist of both Fg and PSMα1 and cannot seed fibrillation. Peptide arrays showed that Fg bound to the N-terminus of PSMα1, while it bound to the entire length of PSMα3 (except the C terminus) and to the C-termini of PSMβ1 and PSMβ2. The latter peptides are all positively charged, while Fg is negatively charged at physiological pH. The positive charges complement Fg's net negative charge of -7.6 at pH 7.4. Fg's ability to inhibit PSM fibrillation reveals a potential host-defense mechanism to prevent bacterial biofilm growth and infections in the human body.

U2 - 10.1021/acsomega.1c02333

DO - 10.1021/acsomega.1c02333

M3 - Journal article

C2 - 34497891

VL - 6

SP - 21960

EP - 21970

JO - ACS Omega

JF - ACS Omega

SN - 2470-1343

IS - 34

ER -