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Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections
The emergence of multidrug-resistant bacterial pathogens is a growing threat to global public health. Here, we report the development and characterization of a panel of nine–amino acid residue synthetic peptides that display potent antibacterial activity and the ability to disrupt preestablished mic...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942841/ https://www.ncbi.nlm.nih.gov/pubmed/36649429 http://dx.doi.org/10.1073/pnas.2219679120 |
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author | Chou, Shuli Guo, Huating Zingl, Franz G. Zhang, Shiqing Toska, Jonida Xu, Bocheng Chen, Yili Chen, Peisong Waldor, Matthew K. Zhao, Wenjing Mekalanos, John J. Mou, Xiangyu |
author_facet | Chou, Shuli Guo, Huating Zingl, Franz G. Zhang, Shiqing Toska, Jonida Xu, Bocheng Chen, Yili Chen, Peisong Waldor, Matthew K. Zhao, Wenjing Mekalanos, John J. Mou, Xiangyu |
author_sort | Chou, Shuli |
collection | PubMed |
description | The emergence of multidrug-resistant bacterial pathogens is a growing threat to global public health. Here, we report the development and characterization of a panel of nine–amino acid residue synthetic peptides that display potent antibacterial activity and the ability to disrupt preestablished microbial biofilms. The lead peptide (Peptide K6) showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus in culture and in monocultures and mixed biofilms in vitro. Biophysical analysis revealed that Peptide K6 self-assembled into nanostructured micelles that correlated with its strong antibiofilm activity. When surface displayed on the outer membrane protein LamB, two copies of the Peptide K6 were highly bactericidal to Escherichia coli. Peptide K6 rapidly increased the permeability of bacterial cells, and resistance to this toxic peptide occurred less quickly than that to the potent antibiotic gentamicin. Furthermore, we found that Peptide K6 was safe and effective in clearing mixed P. aeruginosa–S. aureus biofilms in a mouse model of persistent infection. Taken together, the properties of Peptide K6 suggest that it is a promising antibiotic candidate and that design of additional short peptides that form micelles represents a worthwhile approach for the development of antimicrobial agents. |
format | Online Article Text |
id | pubmed-9942841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-99428412023-07-17 Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections Chou, Shuli Guo, Huating Zingl, Franz G. Zhang, Shiqing Toska, Jonida Xu, Bocheng Chen, Yili Chen, Peisong Waldor, Matthew K. Zhao, Wenjing Mekalanos, John J. Mou, Xiangyu Proc Natl Acad Sci U S A Biological Sciences The emergence of multidrug-resistant bacterial pathogens is a growing threat to global public health. Here, we report the development and characterization of a panel of nine–amino acid residue synthetic peptides that display potent antibacterial activity and the ability to disrupt preestablished microbial biofilms. The lead peptide (Peptide K6) showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus in culture and in monocultures and mixed biofilms in vitro. Biophysical analysis revealed that Peptide K6 self-assembled into nanostructured micelles that correlated with its strong antibiofilm activity. When surface displayed on the outer membrane protein LamB, two copies of the Peptide K6 were highly bactericidal to Escherichia coli. Peptide K6 rapidly increased the permeability of bacterial cells, and resistance to this toxic peptide occurred less quickly than that to the potent antibiotic gentamicin. Furthermore, we found that Peptide K6 was safe and effective in clearing mixed P. aeruginosa–S. aureus biofilms in a mouse model of persistent infection. Taken together, the properties of Peptide K6 suggest that it is a promising antibiotic candidate and that design of additional short peptides that form micelles represents a worthwhile approach for the development of antimicrobial agents. National Academy of Sciences 2023-01-17 2023-01-24 /pmc/articles/PMC9942841/ /pubmed/36649429 http://dx.doi.org/10.1073/pnas.2219679120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Biological Sciences Chou, Shuli Guo, Huating Zingl, Franz G. Zhang, Shiqing Toska, Jonida Xu, Bocheng Chen, Yili Chen, Peisong Waldor, Matthew K. Zhao, Wenjing Mekalanos, John J. Mou, Xiangyu Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections |
title | Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections |
title_full | Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections |
title_fullStr | Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections |
title_full_unstemmed | Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections |
title_short | Synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections |
title_sort | synthetic peptides that form nanostructured micelles have potent antibiotic and antibiofilm activity against polymicrobial infections |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9942841/ https://www.ncbi.nlm.nih.gov/pubmed/36649429 http://dx.doi.org/10.1073/pnas.2219679120 |
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