Grant: Travel Awards - Institute Community Support

Cystic Fibrosis (CF) is an inherited life-limiting disease affecting approximately 4,000 Canadians. The mortality observed in CF patients is predominantly due to recurrent bacterial infections and chronic inflammation, which eventually cause respiratory failure. Our lab's research is focused on the bacterium Pseudomonas aeruginosa (PA), an opportunistic pathogen that responds poorly to antibiotic treatments and has been linked to accelerated disease progression in CF. While PA is traditionally considered to be an extracellular pathogen, our lab has found evidence of intracellular PA in CF patient lung samples, indicating that PA might persist intracellularly. An intracellular reservoir might offer a growth advantage to bacteria, as they would be less succeptible to antibiotic treatments and clearance through the host immune system. In this project, we examine which bacterial factors promote an intracellular PA lifestyle by infecting immortalized airway cells with PA strains deficient in certain bacterial factors and identifying which strains are particularly persistant intracellularly. Preliminary results suggest that strains that are deficient in factors that are commonly lost in chronic PA isolates increase internalization of PA into airway cells as well as PA persistence. In conclusion, our findings suggest that typically "chronic" PA adaptations promote an intracellular lifestyle. This might be a possible explanation for why some PA strains are particularly persistent and eventually develop chronic infections. Targeting these "chronic" PA factors might decrease PA persistence and increase antibiotic eradication therapy efficacy, potentially leading to decreased mortality in CF patients.