Investigating bacteriophage therapy to treat pleural infection

Supervisors:

• Professor Dominick Shaw  des21@le.ac.uk
• Dr Spyridon Megremis  sm1219@leicester.ac.uk

Project:

Background
A pleural infection (known as empyema) occurs when bacteria enter the space between the lungs and chest wall. They have serious outcomes with a 10% 30-day mortality rate. Management typically involves drainage and prolonged broad-spectrum antibiotics.

Aim
This novel cross disciplinary project combines expertise within respiratory medicine, based at the Leicester NIHR Biomedical Research Centre (BRC) and Department of Respiratory Sciences with cutting edge technologies at the Becky Mayer Centre for Phage Research (BMCPR) and sets out to understand whether bacteriophage therapy can be used to treat bacterial infections in the pleural space.

Plan
i) characterise the microbial composition of pleural infections using culture-dependent approaches and molecular typing
ii) test the in vitro efficacy of lytic bacteriophages against bacterial isolates obtained from pleural fluid
iii) Perform ex vivo bacteriophage treatment on infected pleural fluid, from patients at the Glenfield Hospital.

Student support
Via a multidisciplinary team of supervisors and the infrastructure provided by the BMCPR, the institute of precision health (IPH), and the BRC. The BRC offers outstanding training in experiental medicine collaborating with the existing local doctoral training programmes and development pathways. 

The successful applicant will gain skills in bacterial culture, microbiome analysis, bacteriophage characterisation and infection, mass spectrometry, pharmacokinetics, data handling and analysis. The student will develop skills in leadership, management, and collegiality by supervising undergraduate students and by engaging in research meetings, seminars and journal clubs. 

The student will participate in patient outreach programmes promoting phage therapy in lung disease and will present data in national and international scientific meetings and prepare publications using open data and reproducible research. 

Both the BMPCR and BRC are led by world-leading experts in phage biology and respiratory medicine.

References:

1. Elsheikh A, Bhatnagar M, Rahman NM. Diagnosis and management of pleural infection. Breathe (Sheff). 2023 Dec;19(4):230146. doi: 10.1183/20734735.0146-2023.
2. Roberts ME, Rahman NM, Maskell NA, Bibby AC, Blyth KG, Corcoran JP, Edey A, Evison M, de Fonseka D, Hallifax R, Harden S, Lawrie I, Lim E, McCracken DJ, Mercer R, Mishra EK, Nicholson AG, Noorzad F, Opstad K, Parsonage M, Stanton AE, Walker S; BTS Pleural Guideline Development Group. British Thoracic Society Guideline for pleural disease. Thorax. 2023 Jul;78(Suppl 3):s1-s42. doi: 10.1136/thorax-2022-219784