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The Study and Application of Membrane Binding Supramolecular Self-associating Amphiphiles

Boles, Jessica Emily (2022) The Study and Application of Membrane Binding Supramolecular Self-associating Amphiphiles. Doctor of Philosophy (PhD) thesis, University of Kent,. (doi:10.22024/UniKent/01.02.97167) (KAR id:97167)

Language: English

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With the looming threat of antimicrobial resistance (AMR) and the distinct absence of new antimicrobial agents on the market, the development of novel therapeutic treatments against AMR bacteria is vital. The work detailed herein demonstrates the potential for supramolecular self-associating amphiphiles (SSAs) to act as the first anionic antimicrobial potentiator of novobiocin (52) and rifampicin (53) against ESKAPE pathogen Pseudomonas aeruginosa. The most effective combination offered a dramatic 8-fold decrease of the MIC of novobiocin (52), from 3.2 mM to 0.4 mM in the presence of a non-inhibitory SSA concentration. Extensive physicochemical characterisation of SSA/antimicrobial interactions offer explanations for the observed synergistic behaviour.

This thesis validates the hypothesis that SSAs are bacterial membrane disruptors through the employment of fluorescence spectroscopy. The urea benzothiazole SSAs were found to exhibit the highest level of broad range vesicle lysis, however a lack of correlation was observed between vesicle lysis and selective SSA: phospholipid interaction. The ability for SSAs to induce membrane fluidity was explored, revealing the carboxylate moiety over a sulfonate can selectively increase the membrane fluidity of bacterial model membranes over eukaryotic. Finally, a patch clamp method was optimised, providing insight into the potential transport mechanism of SSAs in the presence of an anionophore.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Hiscock, Jennifer
DOI/Identification number: 10.22024/UniKent/01.02.97167
Uncontrolled keywords: Amphiphiles; microbiology
Subjects: Q Science > QR Microbiology
Divisions: Divisions > Division of Natural Sciences > Chemistry and Forensics
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 28 Sep 2022 14:10 UTC
Last Modified: 29 Sep 2022 14:00 UTC
Resource URI: (The current URI for this page, for reference purposes)
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