An in vitro evaluation of novel strategies and compounds to target Pseudomonas aeruginosa

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Grant, Gary D

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Zunk, Matthew S

Cheesman, Matthew

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2023-08-23
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Abstract

Background. Antimicrobial resistance is a significant global threat associated with increased mortality. Pseudomonas aeruginosa is a critically prioritised organism needing new antimicrobials with unique mechanisms. Multidrug-resistant P. aeruginosa strains are becoming increasingly burdensome and justify the need for developing new antipseudomonal antibiotics. Traditional antibiotic drug discovery strategies have yet to deliver a pipeline of novel antipseudomonal antibiotics. It has become imperative to adopt new drug discovery strategies to develop novel lead compounds before these pathogens become resistant to all clinically available antibiotics. This study investigates two important drug targets to identify novel antipseudomonal antibiotics. The research aims and hypothesis. This project aimed to evaluate a series of novel compounds that could interfere with new drug targets in P. aeruginosa and investigate their ability to potentiate the activities of existing antipseudomonal antibiotics. The P. aeruginosa drug targets of interest in this project included the enzyme MraY and the resistance-nodulation-division efflux pumps. This study included a series of synthesised and commercially available compounds belonging to muraymycins and phenazine compound classes. It was hypothesised that inhibiting these drug targets with these compounds would significantly enhance the activities of existing antipseudomonal antibiotics irrespective of P. aeruginosa strain. [...]

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Thesis (PhD Doctorate)

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Doctor of Philosophy (PhD)

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School of Pharmacy & Med Sci

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The author owns the copyright in this thesis, unless stated otherwise.

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Subject

antimicrobial resistance

Pseudomonas aeruginosa

efflux pump inhibitors

muraymycins

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