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

Given the high levels of resistance in Gram-negative bacteria, phage therapy is garnering increasing attention. In Germany, a clinical study is already underway investigating a phage cocktail for the treatment of Pseudomonas aeruginosa in cystic fibrosis (CF) patients. In our study, we examined susceptibility to virulent phages and the PF1-like prophage and antimicrobial profiles and of P. aeruginosa isolates from a local cystic fibrosis cohort to identify correlations and lysogenic conversion of the prophegs. Consistent with other studies, prophage Pf4 is the most prevalent in this cohort and is activated in the absence of other influences during biofilm formation. These phages can be transferred to other strains that do not contain Pf1-like prophages, thereby influencing the dynamics of bacterial populations in the CF lung. This also rapidly leads to the emergence of a subpopulation resistant to the virulent phages, potentially complicating phage therapy. However, this subset also becomes more susceptible to most antibiotics commonly used in CF, which could be a useful treatment strategy. Interestingly, this bacterial subset lost its susceptibility to colistin, an important inhaled antibiotic in CF, which could lead to treatment failure. Our research highlights both the difficulties and potential strategies to improve treatment options for CF patients.