Dilem Ruhluel

I am currently a PhD Student at the Institute of Infection, Veterinary and Ecological Sciences at the University of Liverpool. I completed my undergraduate degree at the University of Southampton where I obtained my BSc in Biomedical Sciences. Following this I completed my MSc in Medical Microbiology at the University of Manchester. My MSc research project focussed on selection pressure of antibiotics on polymicrobial biofilms in the content of diabetic foot infections.

Pseudomonas aeruginosa (Pa) is a key pathogen in people with cystic fibrosis (CF) and non-CF bronchiectasis. Pa lung infections are the single biggest cause of mortality in CF. During early infection, Pa adapts to the respiratory environment, leading to chronic, difficult to treat infections. Drivers of adaptation to the lung are poorly understood. Understanding Pa in-host adaptation would facilitate novel diagnosis and treatment approaches and help in the fight against accelerating antimicrobial resistance (AMR). Robust in vitro models for carrying out such studies are not available to the research community. Recent work from my project supervisors identified that (i) the nasopharynx acts as a protective niche, facilitating Pa adaptation to the host, (ii) host immune pressures lead to bacterial adaptations that may influence the emergence of AMR, even in the absence of antibiotic treatment, and (iii) mutations leading to in vitro susceptibility to antibiotics may not confer susceptibility in the more relevant in vivo environments of nasopharynx or lung.

In vivo models do not allow investigation of nasopharynx and lungs in isolation, making it impossible to determine the impact of bacterial evolution within nasopharynx on subsequent lung infection. Currently available in vitro models are inadequate for these studies as culture conditions are a poor reflection of the respiratory tract environment. Therefore, the aim of this PhD project is to generate and characterise culture media reproducing key features of the upper airways (nasopharynx) and lower airways (lungs) for the study of bacterial evolution and virulence. This will reduce usage of animals for the purposes of experimental evolution and virulence screening, and also offer reduction and replacement opportunities for therapeutic screening and dose testing, and investigation of host-pathogen interactions.