Unveiling Lytic Bacteriophages as Promising Biotherapeutics for the Control of Multidrug-Resistant Pseudomonas aeruginosa

Background/Objectives: Bacteriophages are considered promising alternatives for the treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections. Methods: Five bacteriophages with lytic activity against MDR P. aeruginosa were isolated from lake and sewage samples and characterized for their biological properties, host range, and efficacy in biofilm and in vitro infection models. Results: The phages displayed broad host ranges, producing zones of lysis in 40–53% of MDR isolates. The average burst size was 112 ± 70 PFU per cell. All phages, either individually or in combination, inhibited biofilm formation and were capable of disrupting preformed biofilms. While treatment with single phages led to bacterial regrowth, the cocktail of all five phages achieved complete bacterial lysis with no regrowth observed. In an in vitro wound and burn infection model, the phage cocktail significantly enhanced cell proliferation and promoted healing. Transmission electron microscopy (TEM) analysis identified phage PA2 as a Myovirus based on its morphology. Conclusions: The phage isolates demonstrated strong activity in multiple in vitro models, effectively targeting both planktonic and biofilm-associated P. aeruginosa. Notably, the five-phage combination prevented the emergence of bacterial resistance, supporting its potential as a biocontrol strategy against MDR P. aeruginosa.