Bridging bench and bedside: translational omics of Pseudomonas aeruginosa to validate physiologically relevant models of chronic respiratory infection in cystic fibrosis

While culturing the opportunistic pathogen Pseudomonas aeruginosa in standard bacterial culture media has provided fundamental insights into its pathological properties such as virulence and antibiotic resistance, growing evidence suggests that these conditions fail to accurately reflect the in vivo bacterial physiology. In the lungs of people living with cystic fibrosis (pwCF), where P. aeruginosa is a major contributor to the disease process, bacteria reside within a complex physicochemical environment that drives their behaviour. Until recently, efforts to evaluate how well laboratory models mimic these in vivo conditions were hampered by limited data on the physiology of P. aeruginosa during chronic cystic fibrosis (CF) lung infections. However, several omics-based studies have now successfully characterised P. aeruginosa from human CF sputum, revealing unique adaptation patterns associated within this niche. This data enables evaluating the physiological relevance of in vitro and in vivo model systems, hereby highlighting the usefulness (and limitations) of models that mimic aspects of the physicochemical in vivo environment for studying P. aeruginosa infections in CF. In this review, we summarise a range of models of P. aeruginosa infection, including artificial sputum medium, air–liquid interface cell culture, ex vivo pig lung and mouse models, that have been evaluated for their physiological resemblance using omics-based approaches. We also address the current lack of proteomic and metabolomic validation approaches and outline key considerations and future directions to guide the continued refinement of experimental model systems.