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Title: Nanotechnology approaches to combat antimicrobial resistance : novel therapeutics and diagnostics
Author: Bennett, Isabel Diana
ISNI:       0000 0004 8508 3000
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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Antimicrobial resistance (AMR) is a global issue caused by misuse of antibiotics and a lack of new antibiotics coming to market. Combating the development of AMR requires the development of new antimicrobial agents to treat bacterial infections and better diagnostic tools for improved stewardship. This thesis describes novel approaches to address these issues using nanotechnology. The main technique employed in these studies was atomic force microscopy (AFM), used in both conventional imaging mode and in an innovative sensing capacity. From a therapeutic perspective, the mechanism of action of novel antimicrobial structures (protein / DNA) were studied, using real-time imaging on model membranes and live E. coli cells. Nanometre resolution was achieved on both systems, allowing rapid membrane poration and subsequent cell death to be observed for a de novo designed antimicrobial peptide and a pioneering antimicrobial DNA-lipid origami structure. In addition, this thesis describes the first visualisation of the Membrane Attack Complex (MAC) on live bacterial cells showing remarkable similarity with the recently solved cryo-EM structure. In working to develop novel phenotypic diagnostic tools for AMR, we report on a novel antibiotic susceptibility testing (AST) device. This device uses single cell optical interference to provide a rapid (∼45 min) and simple measure of the effect of antimicrobials on suspended bacterial cells. Homebuilt code was developed to analyse datasets, allowing antibiotic sensitivity to be systematically determined for lab and clinical strains of E. coli. This thesis provides insights into a number of potential avenues to pursue in the face of increasing AMR, with future work entailing moving the described from the lab closer to clinical use.
Supervisor: McKendry, R. ; Pyne, A. ; Abubakar, I. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available