Investigating Novel Antimicrobial Strategies to Target Mycobacterium abscessus Infections

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.