Physical Determinants of Amyloid Assembly in Biofilm Formation

ABSTRACT A wide range of bacterial pathogens have been shown to form biofilms, which significantly increase their resistance to environmental stresses, such as antibiotics, and are thus of central importance in the context of bacterial diseases. One of the major structural components of these bacter...

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Autores principales:	Maria Andreasen, Georg Meisl, Jonathan D. Taylor, Thomas C. T. Michaels, Aviad Levin, Daniel E. Otzen, Matthew R. Chapman, Christopher M. Dobson, Steve J. Matthews, Tuomas P. J. Knowles
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	biofilms functional bacterial amyloids protein aggregation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ba447dbb4f3b48ca9ad7f0012ba4af9b
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spelling	oai:doaj.org-article:ba447dbb4f3b48ca9ad7f0012ba4af9b2021-11-15T15:55:14ZPhysical Determinants of Amyloid Assembly in Biofilm Formation10.1128/mBio.02279-182150-7511https://doaj.org/article/ba447dbb4f3b48ca9ad7f0012ba4af9b2019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02279-18https://doaj.org/toc/2150-7511ABSTRACT A wide range of bacterial pathogens have been shown to form biofilms, which significantly increase their resistance to environmental stresses, such as antibiotics, and are thus of central importance in the context of bacterial diseases. One of the major structural components of these bacterial biofilms are amyloid fibrils, yet the mechanism of fibril assembly and its importance for biofilm formation are currently not fully understood. By studying fibril formation in vitro, in a model system of two common but unrelated biofilm-forming proteins, FapC from Pseudomonas fluorescens and CsgA from Escherichia coli, we found that the two proteins have a common aggregation mechanism. In both systems, fibril formation proceeds via nucleated growth of linear fibrils exhibiting similar measured rates of elongation, with negligible fibril self-replication. These similarities between two unrelated systems suggest that convergent evolution plays a key role in tuning the assembly kinetics of functional amyloid fibrils and indicates that only a narrow window of mechanisms and assembly rates allows for successful biofilm formation. Thus, the amyloid assembly reaction is likely to represent a means for controlling biofilm formation, both by the organism and by possible inhibitory drugs. IMPORTANCE Biofilms are generated by bacteria, embedded in the formed extracellular matrix. The biofilm's function is to improve the survival of a bacterial colony through, for example, increased resistance to antibiotics or other environmental stresses. Proteins secreted by the bacteria act as a major structural component of this extracellular matrix, as they self-assemble into highly stable amyloid fibrils, making the biofilm very difficult to degrade by physical and chemical means once formed. By studying the self-assembly mechanism of the fibrils from their monomeric precursors in two unrelated bacteria, our experimental and theoretical approaches shed light on the mechanism of functional amyloid assembly in the context of biofilm formation. Our results suggest that fibril formation may be a rate-limiting step in biofilm formation, which in turn has implications on the protein self-assembly reaction as a target for potential antibiotic drugs.Maria AndreasenGeorg MeislJonathan D. TaylorThomas C. T. MichaelsAviad LevinDaniel E. OtzenMatthew R. ChapmanChristopher M. DobsonSteve J. MatthewsTuomas P. J. KnowlesAmerican Society for Microbiologyarticlebiofilmsfunctional bacterial amyloidsprotein aggregationMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	biofilms functional bacterial amyloids protein aggregation Microbiology QR1-502
spellingShingle	biofilms functional bacterial amyloids protein aggregation Microbiology QR1-502 Maria Andreasen Georg Meisl Jonathan D. Taylor Thomas C. T. Michaels Aviad Levin Daniel E. Otzen Matthew R. Chapman Christopher M. Dobson Steve J. Matthews Tuomas P. J. Knowles Physical Determinants of Amyloid Assembly in Biofilm Formation
description	ABSTRACT A wide range of bacterial pathogens have been shown to form biofilms, which significantly increase their resistance to environmental stresses, such as antibiotics, and are thus of central importance in the context of bacterial diseases. One of the major structural components of these bacterial biofilms are amyloid fibrils, yet the mechanism of fibril assembly and its importance for biofilm formation are currently not fully understood. By studying fibril formation in vitro, in a model system of two common but unrelated biofilm-forming proteins, FapC from Pseudomonas fluorescens and CsgA from Escherichia coli, we found that the two proteins have a common aggregation mechanism. In both systems, fibril formation proceeds via nucleated growth of linear fibrils exhibiting similar measured rates of elongation, with negligible fibril self-replication. These similarities between two unrelated systems suggest that convergent evolution plays a key role in tuning the assembly kinetics of functional amyloid fibrils and indicates that only a narrow window of mechanisms and assembly rates allows for successful biofilm formation. Thus, the amyloid assembly reaction is likely to represent a means for controlling biofilm formation, both by the organism and by possible inhibitory drugs. IMPORTANCE Biofilms are generated by bacteria, embedded in the formed extracellular matrix. The biofilm's function is to improve the survival of a bacterial colony through, for example, increased resistance to antibiotics or other environmental stresses. Proteins secreted by the bacteria act as a major structural component of this extracellular matrix, as they self-assemble into highly stable amyloid fibrils, making the biofilm very difficult to degrade by physical and chemical means once formed. By studying the self-assembly mechanism of the fibrils from their monomeric precursors in two unrelated bacteria, our experimental and theoretical approaches shed light on the mechanism of functional amyloid assembly in the context of biofilm formation. Our results suggest that fibril formation may be a rate-limiting step in biofilm formation, which in turn has implications on the protein self-assembly reaction as a target for potential antibiotic drugs.
format	article
author	Maria Andreasen Georg Meisl Jonathan D. Taylor Thomas C. T. Michaels Aviad Levin Daniel E. Otzen Matthew R. Chapman Christopher M. Dobson Steve J. Matthews Tuomas P. J. Knowles
author_facet	Maria Andreasen Georg Meisl Jonathan D. Taylor Thomas C. T. Michaels Aviad Levin Daniel E. Otzen Matthew R. Chapman Christopher M. Dobson Steve J. Matthews Tuomas P. J. Knowles
author_sort	Maria Andreasen
title	Physical Determinants of Amyloid Assembly in Biofilm Formation
title_short	Physical Determinants of Amyloid Assembly in Biofilm Formation
title_full	Physical Determinants of Amyloid Assembly in Biofilm Formation
title_fullStr	Physical Determinants of Amyloid Assembly in Biofilm Formation
title_full_unstemmed	Physical Determinants of Amyloid Assembly in Biofilm Formation
title_sort	physical determinants of amyloid assembly in biofilm formation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/ba447dbb4f3b48ca9ad7f0012ba4af9b
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Physical Determinants of Amyloid Assembly in Biofilm Formation

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