Temperate bacteriophage induced in Pseudomonas aeruginosa biofilms can modulate bacteriophage and antibiotic resistance

Given the high resistance levels in Gram-negative bacteria, phage therapy is receiving increasing attention. In Germany, a clinical study is already underway evaluate a phage cocktail for treating Pseudomonas aeruginosa in cystic fibrosis (CF) patients. In this context, we investigated the prevalence of PF1-like prophages in P. aeruginosa isolates from a local CF cohort, their ability to undergo lytic conversion during biofilm formation, and the resulting impact on the resistance profile of the P. aeruginosa population. Consistent with other studies, prophage Pf4 was the most prevalent in this cohort and became during biofilm formation even in the absence of external triggers. This lytic conversion rapidly generated a subpopulation resistant to the virulent phages, potentially complicating phage therapy. However, this subpopulation also became more susceptible to most antibiotics commonly used in CF, suggesting a potential therapeutic opportunity. Interestingly, this bacterial subset lost its susceptibility to colistin, an important inhaled antibiotic in CF, which could increase the risk of treatment failure. These findings underscore both the challenges and potential strategies for improving treatment outcomes in CF patients.