Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation

Thorbjørn V Sønderby; Nikolaos N Louros; Ladan Khodaparast; Laleh Khodaparast; Daniel J Madsen; William P Olsen; Nele Moonen; Madhu Nagaraj; Vita Sereikaite; Kristian Strømgaard; Frederic Rousseau; Joost Schymkowitz; Daniel E Otzen

doi:10.1016/j.jmb.2023.168039

Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation

Thorbjørn V Sønderby, Nikolaos N Louros, Ladan Khodaparast, Laleh Khodaparast, Daniel J Madsen, William P Olsen, Nele Moonen, Madhu Nagaraj, Vita Sereikaite, Kristian Strømgaard, Frederic Rousseau, Joost Schymkowitz, Daniel E Otzen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

4 Citations (Scopus)

Abstract

Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive amyloid formation. Here, we demonstrate the use of aggregation-modulating peptides to knock down CsgA protein into aggregates with low stability and altered morphology. Remarkably, these CsgA-peptides also modulate fibrillation of the unrelated functional amyloid protein FapC from Pseudomonas, possibly through recognition of FapC segments with structural and sequence similarity with CsgA. The peptides also reduce the level of biofilm formation in E. coli and P. aeruginosa, demonstrating the potential for selective amyloid targeting to combat bacterial biofilm.

Original language	English
Article number	168039
Journal	Journal of Molecular Biology
Volume	435
Issue	11
Pages (from-to)	168039
ISSN	0022-2836
DOIs	https://doi.org/10.1016/j.jmb.2023.168039
Publication status	Published - 1 Jun 2023

Keywords

amyloid inhibition
biofilm
functional bacterial amyloid
modulation
peptides

Access to Document

10.1016/j.jmb.2023.168039Licence: CC BY

1-s2.0-S0022283623000955-mainFinal published version, 4.02 MBLicence: CC BY

Cite this

Sønderby, T. V., Louros, N. N., Khodaparast, L., Khodaparast, L., Madsen, D. J., Olsen, W. P., Moonen, N., Nagaraj, M., Sereikaite, V., Strømgaard, K., Rousseau, F., Schymkowitz, J., & Otzen, D. E. (2023). Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation. Journal of Molecular Biology, 435(11), 168039. Article 168039. https://doi.org/10.1016/j.jmb.2023.168039

@article{ac85099827ca4c92ba5f609b14754466,

title = "Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation",

abstract = "Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive amyloid formation. Here, we demonstrate the use of aggregation-modulating peptides to knock down CsgA protein into aggregates with low stability and altered morphology. Remarkably, these CsgA-peptides also modulate fibrillation of the unrelated functional amyloid protein FapC from Pseudomonas, possibly through recognition of FapC segments with structural and sequence similarity with CsgA. The peptides also reduce the level of biofilm formation in E. coli and P. aeruginosa, demonstrating the potential for selective amyloid targeting to combat bacterial biofilm.",

keywords = "amyloid inhibition, biofilm, functional bacterial amyloid, modulation, peptides",

author = "S{\o}nderby, {Thorbj{\o}rn V} and Louros, {Nikolaos N} and Ladan Khodaparast and Laleh Khodaparast and Madsen, {Daniel J} and Olsen, {William P} and Nele Moonen and Madhu Nagaraj and Vita Sereikaite and Kristian Str{\o}mgaard and Frederic Rousseau and Joost Schymkowitz and Otzen, {Daniel E}",

year = "2023",

month = jun,

day = "1",

doi = "10.1016/j.jmb.2023.168039",

language = "English",

volume = "435",

pages = "168039",

journal = "Journal of Molecular Biology",

issn = "0022-2836",

publisher = "Academic Press",

number = "11",

}

Sønderby, TV, Louros, NN, Khodaparast, L, Khodaparast, L, Madsen, DJ, Olsen, WP, Moonen, N, Nagaraj, M, Sereikaite, V, Strømgaard, K, Rousseau, F, Schymkowitz, J & Otzen, DE 2023, 'Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation', Journal of Molecular Biology, vol. 435, no. 11, 168039, pp. 168039. https://doi.org/10.1016/j.jmb.2023.168039

Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation. / Sønderby, Thorbjørn V; Louros, Nikolaos N; Khodaparast, Ladan et al.
In: Journal of Molecular Biology, Vol. 435, No. 11, 168039, 01.06.2023, p. 168039.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation

AU - Sønderby, Thorbjørn V

AU - Louros, Nikolaos N

AU - Khodaparast, Ladan

AU - Khodaparast, Laleh

AU - Madsen, Daniel J

AU - Olsen, William P

AU - Moonen, Nele

AU - Nagaraj, Madhu

AU - Sereikaite, Vita

AU - Strømgaard, Kristian

AU - Rousseau, Frederic

AU - Schymkowitz, Joost

AU - Otzen, Daniel E

PY - 2023/6/1

Y1 - 2023/6/1

N2 - Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive amyloid formation. Here, we demonstrate the use of aggregation-modulating peptides to knock down CsgA protein into aggregates with low stability and altered morphology. Remarkably, these CsgA-peptides also modulate fibrillation of the unrelated functional amyloid protein FapC from Pseudomonas, possibly through recognition of FapC segments with structural and sequence similarity with CsgA. The peptides also reduce the level of biofilm formation in E. coli and P. aeruginosa, demonstrating the potential for selective amyloid targeting to combat bacterial biofilm.

AB - Functional bacterial amyloid provides structural stability in biofilm, making it a promising target for anti-biofilm therapeutics. Fibrils formed by CsgA, the major amyloid component in E. coli are extremely robust and can withstand very harsh conditions. Like other functional amyloids, CsgA contains relatively short aggregation-prone regions (APR) which drive amyloid formation. Here, we demonstrate the use of aggregation-modulating peptides to knock down CsgA protein into aggregates with low stability and altered morphology. Remarkably, these CsgA-peptides also modulate fibrillation of the unrelated functional amyloid protein FapC from Pseudomonas, possibly through recognition of FapC segments with structural and sequence similarity with CsgA. The peptides also reduce the level of biofilm formation in E. coli and P. aeruginosa, demonstrating the potential for selective amyloid targeting to combat bacterial biofilm.

KW - amyloid inhibition

KW - biofilm

KW - functional bacterial amyloid

KW - modulation

KW - peptides

UR - http://www.scopus.com/inward/record.url?scp=85165677584&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2023.168039

DO - 10.1016/j.jmb.2023.168039

M3 - Journal article

C2 - 37330291

SN - 0022-2836

VL - 435

SP - 168039

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 11

M1 - 168039

ER -

Sequence-targeted Peptides Divert Functional Bacterial Amyloid Towards Destabilized Aggregates and Reduce Biofilm Formation

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this