T-Wells Group - Bacterial infection and treatment

About

Our research aims to understand and disrupt the mechanisms used by bacteria to manipulate the host immune system during disease. We focus on bacteria that cause chronic lung infections such as Pseudomonas aeruginosa and Burkholderia cenocepacia. Our research uses a mixture of molecular microbiology, immunology, and genomic approaches.

Dr Wells’s original work in the field of host- pathogen interactions during chronic lung infection has led to several key insights and direct translation to the clinic.

Antibody dependent enhancement of bacterial infection: Antibodies usually protect against bacterial infection, however Dr Wells' work has identified ‘cloaking antibodies’ in patients who have Pseudomonas aeruginosa infections. Cloaking antibodies paradoxically prevent immune killing of patient's bacterial strains. Importantly, high titres of cloaking antibodies has been associated with worse lung function and patient outcomes in people with cystic fibrosis, bronchiectasis and post-lung transplant. These antibodies are also prevalent in acute Pseudomonas infections such as bacteraemia.

Novel treatment of multi-drug resistant Pseudomonas aeruginosa lung infection: As cloaking antibodies (cAbs) protect bacteria from immune killing, we hypothesised that cAb removal would restore normal immune killing. Three patients with chronic P. aeruginosa infections and cAb, who had exhausted all standard treatment options have now been treated via plasmapheresis. This treatment removes all antibody, including cAbs from the patients. After treatment, P. aeruginosa was undetectable in all patients, inflammatory markers were normal and lung function increased. As these patients had strains displaying resistance to many antibiotics used clinically, this is a novel treatment method for multi-drug resistant infections.