Polymers for quorum sense interference

The synthetic polymers reported in this thesis are able to bind the small molecule autoinducer-2 (AI-2) in the Quorum Sense (QS) pathways of the marine organism with high affinity, and some of the polymers are also able to sequester rapidly the same bacteria from suspension. Specifically, the Alizar...

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Main Author: Xue, Xuan
Format: Thesis (University of Nottingham only)
Language:English
Published: 2013
Subjects:
Online Access:https://eprints.nottingham.ac.uk/13060/
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author Xue, Xuan
author_facet Xue, Xuan
author_sort Xue, Xuan
building Nottingham Research Data Repository
collection Online Access
description The synthetic polymers reported in this thesis are able to bind the small molecule autoinducer-2 (AI-2) in the Quorum Sense (QS) pathways of the marine organism with high affinity, and some of the polymers are also able to sequester rapidly the same bacteria from suspension. Specifically, the Alizarin Red S (AR-S) assay was used to compare binding interactions of boric and boronic acid with diol species, and interactions were further probed by 11B-NMR spectroscopy and Mass spectrometry. Dopamine was considered as a potential AI-2 scavenger for polymeric QS control owing to the high binding affinities for boron. Therefore, poly{N-(3,4-dihydroxyphenethyl) methacrylamide-co-N-[3-(dimethylamino)propyl] methacrylamide} [p(DMAm-c-DMAPMAm)] and poly(3,4-dihydroxy-L-phenylalanine methacrylamide) [p(L-DMAm)] were prepared via Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization and characterized by 1H-NMR spectroscopy. The activities of these catechol polymers and carbohydrate-based poly(β-D-glucosyloxyethyl methacrylate) (p(GlcEMA)) in QS interference was demonstrated by bioluminescence assays with the Vibrio harveyi MM32 strain and by bacterial aggregation experiments. Polymersomes were then investigated as artificial protocells, with a view to establishing polymer vesicle containers as both reservoirs of QS mediated molecules, and of binding QS agents and bacteria. Hydrophobic monomers N-(2-Ethylhexyl) acrylamide [p(2-EHAm)] and N-phenylacrylamide [p(PAm)] were therefore polymerized into block copolymers from p(L-DMAm)-RAFT agents. The membrane permeability of polymersomes was measured via encapsulation and release of dyes, while the morphologies were examined with Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). Polymersomes were also investigated for potency in QS quenching via the bioluminescence assay and bacterial aggregation experiments. Initial studies of a communication feedback loop between bacteria and polymersome-encapsulated QS agents were performed again via bioluminescence assays. The results reveal that the investigated polymersomes exhibit potent activities in QS quenching, and further development might act as components of a synthetic biology approach to combating microbial pathogenicity.
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format Thesis (University of Nottingham only)
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spelling nottingham-130602025-02-28T11:22:55Z https://eprints.nottingham.ac.uk/13060/ Polymers for quorum sense interference Xue, Xuan The synthetic polymers reported in this thesis are able to bind the small molecule autoinducer-2 (AI-2) in the Quorum Sense (QS) pathways of the marine organism with high affinity, and some of the polymers are also able to sequester rapidly the same bacteria from suspension. Specifically, the Alizarin Red S (AR-S) assay was used to compare binding interactions of boric and boronic acid with diol species, and interactions were further probed by 11B-NMR spectroscopy and Mass spectrometry. Dopamine was considered as a potential AI-2 scavenger for polymeric QS control owing to the high binding affinities for boron. Therefore, poly{N-(3,4-dihydroxyphenethyl) methacrylamide-co-N-[3-(dimethylamino)propyl] methacrylamide} [p(DMAm-c-DMAPMAm)] and poly(3,4-dihydroxy-L-phenylalanine methacrylamide) [p(L-DMAm)] were prepared via Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization and characterized by 1H-NMR spectroscopy. The activities of these catechol polymers and carbohydrate-based poly(β-D-glucosyloxyethyl methacrylate) (p(GlcEMA)) in QS interference was demonstrated by bioluminescence assays with the Vibrio harveyi MM32 strain and by bacterial aggregation experiments. Polymersomes were then investigated as artificial protocells, with a view to establishing polymer vesicle containers as both reservoirs of QS mediated molecules, and of binding QS agents and bacteria. Hydrophobic monomers N-(2-Ethylhexyl) acrylamide [p(2-EHAm)] and N-phenylacrylamide [p(PAm)] were therefore polymerized into block copolymers from p(L-DMAm)-RAFT agents. The membrane permeability of polymersomes was measured via encapsulation and release of dyes, while the morphologies were examined with Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). Polymersomes were also investigated for potency in QS quenching via the bioluminescence assay and bacterial aggregation experiments. Initial studies of a communication feedback loop between bacteria and polymersome-encapsulated QS agents were performed again via bioluminescence assays. The results reveal that the investigated polymersomes exhibit potent activities in QS quenching, and further development might act as components of a synthetic biology approach to combating microbial pathogenicity. 2013-07-10 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/13060/1/Full_in_PDF.pdf Xue, Xuan (2013) Polymers for quorum sense interference. PhD thesis, University of Nottingham. SYNTHETIC POLYMER DOPAMINE L-DOPA QUORUM SENSING DUAL ACTIVITY BACTERIAL INFECTION
spellingShingle SYNTHETIC POLYMER
DOPAMINE
L-DOPA
QUORUM SENSING
DUAL ACTIVITY
BACTERIAL INFECTION
Xue, Xuan
Polymers for quorum sense interference
title Polymers for quorum sense interference
title_full Polymers for quorum sense interference
title_fullStr Polymers for quorum sense interference
title_full_unstemmed Polymers for quorum sense interference
title_short Polymers for quorum sense interference
title_sort polymers for quorum sense interference
topic SYNTHETIC POLYMER
DOPAMINE
L-DOPA
QUORUM SENSING
DUAL ACTIVITY
BACTERIAL INFECTION
url https://eprints.nottingham.ac.uk/13060/