Pseudomonas aeruginosa extracellular vesicles affect gene regulation and lung inflammation and immunity in cystic fibrosis.

Abstract

Bacterial extracellular vesicles (EVs) are important mediators of host infection. People with cystic fibrosis (CF) often suffer from chronic infection with Pseudomonas aeruginosa, an opportunistic pathogen. However, the relative abundance of P. aeruginosa is not associated with the onset of increased pulmonary symptoms, known as a pulmonary exacerbation. We hypothesized that the cargo of P. aeruginosa EVs is different at times of baseline wellness and pulmonary exacerbation onset in persons with CF. This is the first study to characterize and compare P. aeruginosa EVs at these two time points, using a novel series of steps to isolate the P. aeruginosa EVs directly from the sputum of persons with CF. Our study found a differential packaging of P. aeruginosa proteins at baseline wellness and pulmonary exacerbation, with six proteins being more frequently present in pulmonary exacerbation samples. In addition, we were able to demonstrate that the P. aeruginosa EVs isolated from the sputum of persons with CF at the time of pulmonary exacerbation induced an inflammatory response in CF human bronchial epithelial cells. These data, while preliminary, support the clinical relevance of P. aeruginosa EVs in influencing gene regulation and lung inflammation and immunity in persons with CF.