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Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes

Here we report the first application of non-bactericidal synthetic polymers to modulate the physiology of a bacterial pathogen. Poly(N-[3-(dimethylamino)propyl] methacrylamide) (P1) and poly(N-(3-aminopropyl)methacrylamide) (P2), cationic polymers that bind to the surface of V. cholerae, the infecti...

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Autores principales: Perez-Soto, Nicolas, Moule, Lauren, Crisan, Daniel N., Insua, Ignacio, Taylor-Smith, Leanne M., Voelz, Kerstin, Fernandez-Trillo, Francisco, Krachler, Anne Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607900/
https://www.ncbi.nlm.nih.gov/pubmed/28970909
http://dx.doi.org/10.1039/c7sc00615b
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author Perez-Soto, Nicolas
Moule, Lauren
Crisan, Daniel N.
Insua, Ignacio
Taylor-Smith, Leanne M.
Voelz, Kerstin
Fernandez-Trillo, Francisco
Krachler, Anne Marie
author_facet Perez-Soto, Nicolas
Moule, Lauren
Crisan, Daniel N.
Insua, Ignacio
Taylor-Smith, Leanne M.
Voelz, Kerstin
Fernandez-Trillo, Francisco
Krachler, Anne Marie
author_sort Perez-Soto, Nicolas
collection PubMed
description Here we report the first application of non-bactericidal synthetic polymers to modulate the physiology of a bacterial pathogen. Poly(N-[3-(dimethylamino)propyl] methacrylamide) (P1) and poly(N-(3-aminopropyl)methacrylamide) (P2), cationic polymers that bind to the surface of V. cholerae, the infectious agent causing cholera disease, can sequester the pathogen into clusters. Upon clustering, V. cholerae transitions to a sessile lifestyle, characterised by increased biofilm production and the repression of key virulence factors such as the cholera toxin (CTX). Moreover, clustering the pathogen results in the minimisation of adherence and toxicity to intestinal epithelial cells. Our results suggest that the reduction in toxicity is associated with the reduction to the number of free bacteria, but also the downregulation of toxin production. Finally we demonstrate that these polymers can reduce colonisation of zebrafish larvae upon ingestion of water contaminated with V. cholerae. Overall, our results suggest that the physiology of this pathogen can be modulated without the need to genetically manipulate the microorganism and that this modulation is an off-target effect that results from the intrinsic ability of the pathogen to sense and adapt to its environment. We believe these findings pave the way towards a better understanding of the interactions between pathogenic bacteria and polymeric materials and will underpin the development of novel antimicrobial polymers.
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spelling pubmed-56079002017-10-02 Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes Perez-Soto, Nicolas Moule, Lauren Crisan, Daniel N. Insua, Ignacio Taylor-Smith, Leanne M. Voelz, Kerstin Fernandez-Trillo, Francisco Krachler, Anne Marie Chem Sci Chemistry Here we report the first application of non-bactericidal synthetic polymers to modulate the physiology of a bacterial pathogen. Poly(N-[3-(dimethylamino)propyl] methacrylamide) (P1) and poly(N-(3-aminopropyl)methacrylamide) (P2), cationic polymers that bind to the surface of V. cholerae, the infectious agent causing cholera disease, can sequester the pathogen into clusters. Upon clustering, V. cholerae transitions to a sessile lifestyle, characterised by increased biofilm production and the repression of key virulence factors such as the cholera toxin (CTX). Moreover, clustering the pathogen results in the minimisation of adherence and toxicity to intestinal epithelial cells. Our results suggest that the reduction in toxicity is associated with the reduction to the number of free bacteria, but also the downregulation of toxin production. Finally we demonstrate that these polymers can reduce colonisation of zebrafish larvae upon ingestion of water contaminated with V. cholerae. Overall, our results suggest that the physiology of this pathogen can be modulated without the need to genetically manipulate the microorganism and that this modulation is an off-target effect that results from the intrinsic ability of the pathogen to sense and adapt to its environment. We believe these findings pave the way towards a better understanding of the interactions between pathogenic bacteria and polymeric materials and will underpin the development of novel antimicrobial polymers. Royal Society of Chemistry 2017-08-01 2017-05-16 /pmc/articles/PMC5607900/ /pubmed/28970909 http://dx.doi.org/10.1039/c7sc00615b Text en This journal is © The Royal Society of Chemistry 2017 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Perez-Soto, Nicolas
Moule, Lauren
Crisan, Daniel N.
Insua, Ignacio
Taylor-Smith, Leanne M.
Voelz, Kerstin
Fernandez-Trillo, Francisco
Krachler, Anne Marie
Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes
title Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes
title_full Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes
title_fullStr Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes
title_full_unstemmed Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes
title_short Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in Vibrio cholerae and downregulate the expression of virulence genes
title_sort engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in vibrio cholerae and downregulate the expression of virulence genes
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5607900/
https://www.ncbi.nlm.nih.gov/pubmed/28970909
http://dx.doi.org/10.1039/c7sc00615b
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