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Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents

Curli amyloid fibrils secreted by Enterobacteriaceae mediate host cell adhesion and contribute to biofilm formation, thereby promoting bacterial resistance to environmental stressors. Here, we present crystal structures of amyloid-forming segments from the major curli subunit, CsgA, revealing steric...

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Autores principales: Perov, Sergei, Lidor, Ofir, Salinas, Nir, Golan, Nimrod, Tayeb- Fligelman, Einav, Deshmukh, Maya, Willbold, Dieter, Landau, Meytal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748439/
https://www.ncbi.nlm.nih.gov/pubmed/31469892
http://dx.doi.org/10.1371/journal.ppat.1007978
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author Perov, Sergei
Lidor, Ofir
Salinas, Nir
Golan, Nimrod
Tayeb- Fligelman, Einav
Deshmukh, Maya
Willbold, Dieter
Landau, Meytal
author_facet Perov, Sergei
Lidor, Ofir
Salinas, Nir
Golan, Nimrod
Tayeb- Fligelman, Einav
Deshmukh, Maya
Willbold, Dieter
Landau, Meytal
author_sort Perov, Sergei
collection PubMed
description Curli amyloid fibrils secreted by Enterobacteriaceae mediate host cell adhesion and contribute to biofilm formation, thereby promoting bacterial resistance to environmental stressors. Here, we present crystal structures of amyloid-forming segments from the major curli subunit, CsgA, revealing steric zipper fibrils of tightly mated β-sheets, demonstrating a structural link between curli and human pathological amyloids. D-enantiomeric peptides, originally developed to interfere with Alzheimer’s disease-associated amyloid-β, inhibited CsgA fibrillation and reduced biofilm formation in Salmonella typhimurium. Moreover, as previously shown, CsgA fibrils cross-seeded fibrillation of amyloid-β, providing support for the proposed structural resemblance and potential for cross-species amyloid interactions. The presented findings provide structural insights into amyloidogenic regions important for curli formation, suggest a novel strategy for disrupting amyloid-structured biofilms, and hypothesize on the formation of self-propagating prion-like species originating from a microbial source that could influence neurodegenerative diseases.
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spelling pubmed-67484392019-09-27 Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents Perov, Sergei Lidor, Ofir Salinas, Nir Golan, Nimrod Tayeb- Fligelman, Einav Deshmukh, Maya Willbold, Dieter Landau, Meytal PLoS Pathog Research Article Curli amyloid fibrils secreted by Enterobacteriaceae mediate host cell adhesion and contribute to biofilm formation, thereby promoting bacterial resistance to environmental stressors. Here, we present crystal structures of amyloid-forming segments from the major curli subunit, CsgA, revealing steric zipper fibrils of tightly mated β-sheets, demonstrating a structural link between curli and human pathological amyloids. D-enantiomeric peptides, originally developed to interfere with Alzheimer’s disease-associated amyloid-β, inhibited CsgA fibrillation and reduced biofilm formation in Salmonella typhimurium. Moreover, as previously shown, CsgA fibrils cross-seeded fibrillation of amyloid-β, providing support for the proposed structural resemblance and potential for cross-species amyloid interactions. The presented findings provide structural insights into amyloidogenic regions important for curli formation, suggest a novel strategy for disrupting amyloid-structured biofilms, and hypothesize on the formation of self-propagating prion-like species originating from a microbial source that could influence neurodegenerative diseases. Public Library of Science 2019-08-30 /pmc/articles/PMC6748439/ /pubmed/31469892 http://dx.doi.org/10.1371/journal.ppat.1007978 Text en © 2019 Perov et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Perov, Sergei
Lidor, Ofir
Salinas, Nir
Golan, Nimrod
Tayeb- Fligelman, Einav
Deshmukh, Maya
Willbold, Dieter
Landau, Meytal
Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
title Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
title_full Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
title_fullStr Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
title_full_unstemmed Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
title_short Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents
title_sort structural insights into curli csga cross-β fibril architecture inspire repurposing of anti-amyloid compounds as anti-biofilm agents
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748439/
https://www.ncbi.nlm.nih.gov/pubmed/31469892
http://dx.doi.org/10.1371/journal.ppat.1007978
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