Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms

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Standard

Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms. / Bleem, Alissa; Christiansen, Gunna; Madsen, Daniel J; Maric, Hans; Strømgaard, Kristian; Bryers, James D; Daggett, Valerie; Meyer, Rikke L; Otzen, Daniel E.

I: Journal of Molecular Biology, Bind 430, Nr. 20, 12.10.2018, s. 3751-3763.

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

Harvard

Bleem, A, Christiansen, G, Madsen, DJ, Maric, H, Strømgaard, K, Bryers, JD, Daggett, V, Meyer, RL & Otzen, DE 2018, 'Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms', Journal of Molecular Biology, bind 430, nr. 20, s. 3751-3763. https://doi.org/10.1016/j.jmb.2018.06.043

APA

Bleem, A., Christiansen, G., Madsen, D. J., Maric, H., Strømgaard, K., Bryers, J. D., Daggett, V., Meyer, R. L., & Otzen, D. E. (2018). Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms. Journal of Molecular Biology, 430(20), 3751-3763. https://doi.org/10.1016/j.jmb.2018.06.043

CBE

Bleem A, Christiansen G, Madsen DJ, Maric H, Strømgaard K, Bryers JD, Daggett V, Meyer RL, Otzen DE. 2018. Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms. Journal of Molecular Biology. 430(20):3751-3763. https://doi.org/10.1016/j.jmb.2018.06.043

MLA

Vancouver

Bleem A, Christiansen G, Madsen DJ, Maric H, Strømgaard K, Bryers JD o.a. Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms. Journal of Molecular Biology. 2018 okt 12;430(20):3751-3763. https://doi.org/10.1016/j.jmb.2018.06.043

Author

Bleem, Alissa ; Christiansen, Gunna ; Madsen, Daniel J ; Maric, Hans ; Strømgaard, Kristian ; Bryers, James D ; Daggett, Valerie ; Meyer, Rikke L ; Otzen, Daniel E. / Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms. I: Journal of Molecular Biology. 2018 ; Bind 430, Nr. 20. s. 3751-3763.

Bibtex

@article{fab62c4fcce6481dbd231c938f99dbe1,
title = "Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms",
abstract = "Amyloids are typically associated with neurodegenerative diseases, but recent research demonstrates that several bacteria utilize functional amyloid fibrils to fortify the biofilm extracellular matrix and thereby resist antibiotic treatments. In Pseudomonas aeruginosa, these fibrils are composed predominantly of FapC, a protein with high sequence conservation among the genera. Previous studies established FapC as the major amyloid subunit, but its mechanism of fibril formation in P. aeruginosa remained largely unexplored. Here, we examine the FapC sequence in greater detail through a combination of bioinformatics and protein engineering, and we identify specific motifs that are implicated in amyloid formation. Sequence regions of high evolutionary conservation tend to coincide with regions of high amyloid propensity, and mutation of amyloidogenic motifs to a designed, non-amyloidogenic motif suppresses fibril formation in a pH-dependent manner. We establish the particular significance of the third repeat motif in promoting fibril formation and also demonstrate emergence of soluble oligomer species early in the aggregation pathway. The insights reported here expand our understanding of the mechanism of amyloid polymerization in P. aeruginosa, laying the foundation for development of new amyloid inhibitors to combat recalcitrant biofilm infections.",
author = "Alissa Bleem and Gunna Christiansen and Madsen, {Daniel J} and Hans Maric and Kristian Str{\o}mgaard and Bryers, {James D} and Valerie Daggett and Meyer, {Rikke L} and Otzen, {Daniel E}",
note = "Copyright {\textcopyright} 2018. Published by Elsevier Ltd.",
year = "2018",
month = oct,
day = "12",
doi = "10.1016/j.jmb.2018.06.043",
language = "English",
volume = "430",
pages = "3751--3763",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press",
number = "20",

}

RIS

TY - JOUR

T1 - Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms

AU - Bleem, Alissa

AU - Christiansen, Gunna

AU - Madsen, Daniel J

AU - Maric, Hans

AU - Strømgaard, Kristian

AU - Bryers, James D

AU - Daggett, Valerie

AU - Meyer, Rikke L

AU - Otzen, Daniel E

N1 - Copyright © 2018. Published by Elsevier Ltd.

PY - 2018/10/12

Y1 - 2018/10/12

N2 - Amyloids are typically associated with neurodegenerative diseases, but recent research demonstrates that several bacteria utilize functional amyloid fibrils to fortify the biofilm extracellular matrix and thereby resist antibiotic treatments. In Pseudomonas aeruginosa, these fibrils are composed predominantly of FapC, a protein with high sequence conservation among the genera. Previous studies established FapC as the major amyloid subunit, but its mechanism of fibril formation in P. aeruginosa remained largely unexplored. Here, we examine the FapC sequence in greater detail through a combination of bioinformatics and protein engineering, and we identify specific motifs that are implicated in amyloid formation. Sequence regions of high evolutionary conservation tend to coincide with regions of high amyloid propensity, and mutation of amyloidogenic motifs to a designed, non-amyloidogenic motif suppresses fibril formation in a pH-dependent manner. We establish the particular significance of the third repeat motif in promoting fibril formation and also demonstrate emergence of soluble oligomer species early in the aggregation pathway. The insights reported here expand our understanding of the mechanism of amyloid polymerization in P. aeruginosa, laying the foundation for development of new amyloid inhibitors to combat recalcitrant biofilm infections.

AB - Amyloids are typically associated with neurodegenerative diseases, but recent research demonstrates that several bacteria utilize functional amyloid fibrils to fortify the biofilm extracellular matrix and thereby resist antibiotic treatments. In Pseudomonas aeruginosa, these fibrils are composed predominantly of FapC, a protein with high sequence conservation among the genera. Previous studies established FapC as the major amyloid subunit, but its mechanism of fibril formation in P. aeruginosa remained largely unexplored. Here, we examine the FapC sequence in greater detail through a combination of bioinformatics and protein engineering, and we identify specific motifs that are implicated in amyloid formation. Sequence regions of high evolutionary conservation tend to coincide with regions of high amyloid propensity, and mutation of amyloidogenic motifs to a designed, non-amyloidogenic motif suppresses fibril formation in a pH-dependent manner. We establish the particular significance of the third repeat motif in promoting fibril formation and also demonstrate emergence of soluble oligomer species early in the aggregation pathway. The insights reported here expand our understanding of the mechanism of amyloid polymerization in P. aeruginosa, laying the foundation for development of new amyloid inhibitors to combat recalcitrant biofilm infections.

U2 - 10.1016/j.jmb.2018.06.043

DO - 10.1016/j.jmb.2018.06.043

M3 - Journal article

C2 - 29964047

VL - 430

SP - 3751

EP - 3763

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 20

ER -