How cystic fibrosis modulator therapy could transform Pseudomonas aeruginosa epidemiology

The advent of cystic fibrosis transmembrane conductance regulator modulators has revolutionized cystic fibrosis (CF) care by restoring epithelial ion transport and improving airway physiology in people with CF. These therapies reduce infection burden, especially from Pseudomonas aeruginosa , through enhanced mucociliary clearance and immune responses. Yet, P. aeruginosa often persists, raising concerns about microbial adaptation. Emerging evidence suggests that modulator-altered airways impose novel selective pressures, favouring mutations in genes linked to biofilm formation, iron metabolism and immune evasion. This may drive the emergence of strains adapted to a ‘hybrid’ airway; neither fully CF-like nor fully healthy. Such adaptations could potentially increase transmissibility or virulence, with implications beyond the CF population. Understanding how pathogens evolve under modulator pressure is essential in this new treatment era. Continued surveillance of microbial dynamics will be key to anticipating shifts in infection risk and informing future clinical and public health strategies.