AMR pathogens in cystic fibrosis: Development of host-relevant models and discovery of antibiotic combinations

Background: The project directly addresses the urgent need for new drugs to treat AMR pathogens Pseudomonas aeruginosa and Mycobacterium abscessus in the lungs of cystic fibrosis (CF) patients. Mycobacterium abscessus is intrinsically resistant to many drugs, thanks to its physiology and to the acquisition of new mechanisms of drug resistance. Little is known about the phenotype of M. abs and its interaction with other bacterial species, particularly P. aeruginosa, in this niche.

Very few new compounds or drug combinations for the treatment of M. abs are in preclinical and clinical development. Therefore, new regimens of antibiotics are urgently required that can successfully treat M. abs but also other bacteria, such as P. aeruginosa, in the CF lung.

Objectives: 1) Apply growth models (including biofilms) and molecular/imaging technologies to study co-culture of P. aeruginosa and M. abscessus 2) Use Raman spectroscopy and multimodal imaging to study the changes in the pathogens 3) Investigate the impact of frontline antibiotics 4) Identify a combination of antibiotics that successfully clear both pathogens.

There is a strong focus on training and interdisciplinary collaborative working in this project. In the first year the student will attend CDT modules and undergo training in spectroscopic/imaging methodologies available at Southampton while engaging with the supervisory team at Porton Down. During years 2-4, the student will develop in vitro co-culture models, perform drug experiments, and characterise biofilms working at Porton Down while working with the UoS supervisory team on utilising and conducting analyses of biofilms using Raman spectroscopy and multimodal imaging/confocal microscopy.

Thus the student will gain transferable skills and develop both experimental and analytical skills across microbiology, characterisation and imaging working across Southampton and Porton Down with an interdisciplinary team.