Cystic Fibrosis (CF) is the most common genetically-inheritable life-threatening disease amongst Caucasians. Patients with CF are susceptible to chronic lung infections, most commonly caused by the bacterium Pseudomonas aeruginosa, and these infections are responsible for most of the morbidity and mortality associated with the disease. CF patients are regularly treated with a cocktail of drugs, including antibiotics. Aggressive antibiotic therapy is required when patients suffer periodic pulmonary exacerbations, usually with two antibiotics for different bacterial target sites.
Antimicrobial resistance (AMR) has become a global challenge with P. aeruginosa being identified by the WHO as one of the top three priority pathogens. Antibiotic stewardship (appropriate use of existing drugs) is crucial. In CF, the choice of antibiotics is often not based on strong evidence, and little is known about whether certain treatments may be less desirable in terms of efficacy or driving resistance, including “collateral” resistance (i.e. resistance to antibiotics other than those used).
The studentship represents a collaboration between researchers at the Universities of Liverpool and Sheffield, to model the impact of antibiotic treatment regime on long-term (collateral) resistance. In this project we will test the hypothesis that antibiotic treatment against P. aeruginosa can be optimised to limit long term resistance with a range of clinically relevant antibiotics. We will achieve this through three aims:
1. To perform experimental in vitro evolution in an artificial sputum medium to determine the impact of treatment on resistance in P. aeruginosa.
2. To collaborate with other disciplines to model and study the wider impact of each treatment regime on long term infections. This will utilise a combination of phenotypic and genetic data.
3. To study the evolution of resistance in existing patient sputum samples from a clinical trial in people with CF.
This project would provide extensive training in P. aeruginosa biology, genomics and in vitro, population and mathematical modelling (supported by all supervisors). This project is a clear example of an interdisciplinary approach to tackle a major issue in healthcare, although a maths background is not essential for this project.
CF is a condition that requires the ultimate personalized medicine. This would be addressed by determining the impact of existing antibiotics in this setting and developing models for the impact of long-term antibiotic use on resistance.
Supervisor details:
Dr J Fothergill https://www.liverpool.ac.uk/infection-and-global-health/staff/jo-fothergill/ @JoJoFoth
Dr Dylan Childs https://www.sheffield.ac.uk/biosciences/people/aps-staff/academic/dylan-childs
Dr K Sharkey https://www.liverpool.ac.uk/mathematical-sciences/staff/kieran-sharkey/
This studentship is a medical microbiology, lab-based project based in the Department of Clinical Infection, Microbiology and Immunology, at the University of Liverpool.
Informal enquiries are welcome and encouraged to be made to Dr Jo Fothergill on [Email Address Removed]
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