Nolan, Victoria Claire (2022). Investigating Novel Antimicrobial Strategies to Target Mycobacterium abscessus Infections. PHD thesis, Aston University.
Abstract
Mycobacterium abscessus is an opportunistic pathogen of increasing importance, especially for individuals with pre-existing lung conditions such as bronchiectasis and cystic fibrosis. The current drug regimen for pulmonary M. abscessus infections requires a lengthy course of multiple antibiotics with severe side effects, usually resulting in poor patient outcomes. Therefore, new and novel strategies to combat these infections are urgently required. New areas of interest are the natural product Manuka honey, as well as metal-ion complexes, such as ruthenium based compounds. We have explored the efficacy of manuka honey against M. abscessus in vitro, as well as against a panel of clinical M. abscessus isolates. Building upon this activity, we assessed the interactions between manuka honey and the front-line antimicrobials amikacin, tobramycin and azithromycin in combination against M. abscessus. The synergy found between manuka honey and amikacin has led to the development of an in vitro nebulisation assay, as a potential new therapy option. We have also investigated the components of manuka honey to identify the active compounds against M. abscessus. This led us to the development of a modified vegan ‘honea’, which gained antimicrobial activity through the addition of the precursors that give rise to the antimicrobial compounds found in honey. Finally, we investigated the potential of novel ruthenium based complexes against M. abscessus and a variety of other bacterial pathogens as a potential new set of antimicrobial compounds. Overall, the work within this thesis demonstrates new antimicrobials and novel strategies to combat severe M. abscessus infections.
Divisions: | College of Health & Life Sciences > School of Biosciences |
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Additional Information: | Copyright © Victoria Claire Nolan, 2022. Victoria Claire Nolan asserts their moral right to be identified as the author of this thesis. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without appropriate permission or acknowledgement. If you have discovered material in Aston Publications Explorer which is unlawful e.g. breaches copyright, (either yours or that of a third party) or any other law, including but not limited to those relating to patent, trademark, confidentiality, data protection, obscenity, defamation, libel, then please read our Takedown Policy and contact the service immediately. Collaborator Acknowledgements: The work within this thesis was funded by Aston University and Give a Child Health Fund, Birmingham. The work within this thesis includes published works, which have been credited in the relevant places and a publications list has been attached. The work presented in Chapter 5 was conducted in conjunction with University of Bradford, and only my own contributions to this collaboration have been reported. All data presented and written content are of my own original work, with no significant contributions to the written text from the co-authors. |
Institution: | Aston University |
Last Modified: | 28 Jun 2024 08:22 |
Date Deposited: | 04 Jul 2023 11:47 |
Completed Date: | 2022 |
Authors: |
Nolan, Victoria Claire
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