Senior Lecturer in Molecular Microbiology
My research focuses on understanding how antibiotics kill bacteria, how this is affected by the host environment, and the development of novel therapeutic approaches to overcome antibiotic resistance and tolerance. This work falls into four main themes:
Understanding how polymyxins kill bacteria. The rise of drug-resistant Gram-negative pathogens has led to the use of polymyxin antibiotics such as colistin as treatments of last resort. However, polymyxins have poor efficacy and are nephrotoxic. Work in my lab is focussed on understanding how colistin kills bacteria, with a view to making this process more efficient and thereby enhancing patient oucomes.
Determining the molecular basis of colistin resistance and hetero-resistance in Gram-negative pathogens. In collaboration with Imperial's Health Protection Research Unit, we are studying the colistin resistance mechanisms of pathogens responsible for hospital-associated infections. Hetero-resistance is particularly challenging since it can be difficult to identify using standard laboratory diagnostics.
Understanding how the host environment affects antibiotic susceptibility. During infection, bacteria are exposed to numerous stresses that can affect susceptibility to antibiotics, as well as host defences. A greater understanding of bacterial stress responses may identify targets for novel therapeutic approaches and provide opportunities to improve antibiotic susceptibility testing.
Novel approaches to overcoming antibiotic resistance. We are developing new therapeutics that increase the susceptibility of bacteria to both antibiotics and host defences in collaboration with Colleagues in the Department of Chemistry. We are also working with collaborators in the Department of Bioengineering to develop new drug delivery systems that will enable us to combat drug-resistant pathogens.
et al., 2020, Staphylococcal DNA repair is required for infection, MBIO, ISSN:2150-7511
et al., 2019, Exploitation of antibiotic resistance as a novel drug target: development of a β-lactamase-activated antibacterial prodrug., Journal of Medicinal Chemistry, Vol:62, ISSN:0022-2623, Pages:4411-4425