Mycobacterium abscessus is an environmental microorganism that has found a deadly niche in the cystic fibrosis (CF) lung. Both adults and children infected with M. abscessus face 18 months of intensive antibiotic intervention, including both intravenous and nebulised formulations which result in severe and traumatic side effects. Furthermore, treatment is often unsuccessful, and patients present with recurrent infections that contribute to the high mortality rate associated with M. abscessus. Additionally, incidence of infections is rising. The bacterial persistence within the lung environment is thought to be attributed to biofilm formation, aided by the thick mucus matrix typical of the CF lung. We have previously developed a 2D in vitro lung model that enables us to assess the efficacy of nebulised antibiotics against M. abscessus. Beyond this, we have identified compounds that potentiate the antibacterial efficacy of known antibiotics when delivered in combination with them. As a next step, we would like to further develop this model into a 3D hydrogel-based system to determine this efficacy in a more physiologically relevant biofilm as would be observed in the CF lung environment. This will provide us with a much clearer understanding of the way in which M. abscessus grows and responds to antibiotic stress within the host lung, and will enable us to further test the efficacy of the potentiator compounds in a cell-free culture system.
This PhD project is part of CDT in Engineered Tissues for Discovery, Industry and Medicine, a partnership between the University of Glasgow, University of Birmingham, Aston University and National University of Ireland Galway. The CDT will train the next generation of interdisciplinary (engineering, chemistry, physics, maths and biology) leaders in developing in vitro tissues, sensing and diagnostics to develop humanised in vitro systems to drive better drug screening.
For more information about the benefits of the programme, funding, eligibility and EDI support please refer to our main CDT advert.
Continue with Facebook
