How do bacteria adapt survive in the lungs of patients with chronic lung infections like bronchiectasis?

Haemophilus influenzae and Pseudomonas aeruginosa are key pathogens in bronchiectasis and other chronic lung diseases like COPD. Chronic infections are associated with decreased quality of life and increased disease severity in patients and antibiotic treatments often fail to clear infections. Within the niche of patient’s lungs, both pathogens are living within complex microenvironments, competing with other bacteria within the microbiome and evading killing by the immune system.

Microbiome analysis has shown Haemophilus and Pseudomonas can exist in high abundances, with little competition from other species, and the opposite is also true. As one species becomes dominant within the microbiome, patients’ symptoms worsen.

An unanswered question in these infections is how bacteria evade the immune system, since bacteria cause the recruitment of immune cells such as neutrophils but are somehow able to survive in an environment rich in inflammatory cells and antimicrobial peptides.

Understanding how H. influenzae or P. aeruginosa are surviving in the lungs, develop chronic infections, and interacting with immune factors may aid the identification of targets for novel antimicrobials in bronchiectasis. Finding ways to enhance “natural” defences against infection, rather than using more and more antibiotics is an attractive strategy to combat antibiotic resistance.

In this project we will investigate the molecular mechanisms by which H. influenzae or P. aeruginosa adapt and survive in the lungs of patients with bronchiectasis. The project will involve culturing clinical isolates and lab strains in vitro in the presence of other bacteria and immune products in a range of microbiological assays to understand variation between bacterial responses, both functionally and at the transcriptional level. Whole genome sequencing will then be used to see genetic difference between strains and detect contributing virulence factors. Any potential virulence factors will then be validated in laboratory strains. Primary neutrophils, and immune cells from patients, will be used to see how virulence factors influence immune responses.

The project will be most suited to a candidate keen to pursue a career in microbiology, bioinformatics and/or translational research involving patients.

The Respiratory research group at the University of Dundee is a world leading centre for translational research into inflammation and infection in respiratory disease. Previous PhD students have won multiple awards and students regularly published in high impact journals.

Start date is negotiable for the right candidate.

Informal enquiries to Professor James D Chalmers j.chalmers@dundee.ac.uk

To apply send CV and cover letter to respiratoryresearchgroup@dundee.ac.uk