Evaluation of the Efficacy of a Recombinant Phage-Lysin Hydrogel on Multi-Drug Resistant Pseudomonas aeruginosa

Background: Multidrug-resistant (MDR) Pseudomonas aeruginosa infections represent a grave public health concern. Bacteriophages (phages) or their lysins can be used as alternatives or complements to antibiotics. Objective: This study was designed to isolate and characterize specific lytic bacteriophages for P. aeruginosa and development of lysine-thermosensitive hydrogel be used as a biomedicine application. Methodology: VITEK-2 Compact System was used for identification of isolated organisms while Kirby-Bauer disc diffusion method was used for antibiotics sensitivity testing. Phages were isolated and their biological kinetic and phenotypic properties were discovered by spotting test and transmission electron microscopy. Gene cloning and lysin effects were tested. A lysin hydrogel formulation was developed. Results: Two specific P. aeruginosa bacteriophages were isolated (BP-PS1) and (BP-PS2). They belong to the Myoviridae family, order Caudovirales. The infectivity rates of BP-PS1 and BP-PS2 were 83% and 91%, respectively. While, a phage cocktail has achieved full infectivity at 100% on the tested MDR isolates. The expressed and purified lytic lysins have been derived from these bacteriophages. They exhibited potent bactericidal activity against P. aeruginosa. The developed lysin hydrogel demonstrated exceptional stability and uniform drug content. The hydrogel exhibited favorable ex vivo skin diffusion characteristics with 84.87% permeation rate, indicating a favorable sustained and controlled drug release. The gel optimal pH level of 6.16 ± 0.1 displayed a pseudo-plastic flow behavior and proved to be easy to apply. Conclusion: This study highlights the immense potential that projects bacteriophage lysin hydrogels as an enzybiotic therapy wherewith to effectively address MDR P. aeruginosa infections. Given the urgency of the antibiotics resistance crisis, the development of innovative treatments like lysin hydrogels offers hope in mitigating the impact of drug-resistant bacterial infections.