Pseudomonas aeruginosa is an opportunistic pathogen that is often found to infect the lungs of patients with Cystic Fibrosis (CF) which leads to a decrease in pulmonary function. In the lungs and digestive system of CF patients, there is a build-up of thick, sticky mucus that provides bacteria such as P. aeruginosa with the ideal conditions for the bacteria to form biofilms and withstand environmental stresses such as antibiotics, and as the disease progresses, these biofilms in conjunction with efflux pumps provide multi-drug resistance to the bacteria leading to the ineffective use of numerous antibiotics. The significant ability of P. aeruginosa to withstand antibiotics through biofilm production and efflux pumps has led to the treatment of P. aeruginosa infections being increasingly difficult. Due to this CF patients require the use of last-resort antibiotics such as colistin which have harmful side effects. The main objectives of this project are to investigate the antibiotic resistance profile of clinical isolates of P. aeruginosa from two different patient groups, one group of patients with CF and the other group of patients with other respiratory infections caused by P. aeruginosa (non-CF) and determine whether isolates from CF patients have enhanced abilities to resist antibiotics and other compounds due to the different environments present in the CF lung in comparison to a non-CF lung, to evaluate potential adjuvant combinations (antibiotics and efflux pump inhibitors) activity against planktonic cells and to test efficient combinations of antibiotics and efflux pump inhibitors on biofilm formation by the use of a diverse range of experimental techniques including; Minimum inhibitory and bactericidal concentration, permeability assays and biofilm assays. The expectation for this research project is that the use of combinational therapies will provide novel antibiotics for CF patients and also decrease the rate of bacterial resistance to newly developed combinational therapies.
