Bacteriophage Therapy Increases Complement-Mediated Lysis of Bacteria and Enhances Bacterial Clearance After Acute Lung Infection With Multidrug-Resistant Pseudomonas aeruginosa

Abstract

Emergence of multidrug-resistant (MDR) bacterial infections is a major problem in clinical medicine. Development of new strategies such as phage therapy may be a novel approach for treatment of life-threatening infections caused by MDR bacteria. A newly isolated phage, MMI-Ps1, with strong lytic activity was used for treatment of acute lung infection with Pseudomonas aeruginosa in a mouse model. Intranasal administration of a single dose of MMI-Ps1 immediately after infection provided a significant level of protection and increased the survival duration. Moreover, treatment of infected mice with phage as late as 12 hours after infection was still protective. Our in vitro results are the first to show the synergistic elimination of serum-resistant Pseudomonas strains by phage and complement. Phage therapy increases the efficacy of complement-mediated lysis of serum-resistant P. aeruginosa strains, indicating the importance of an intact complement system in clearing Pseudomonas infection during phage therapy.

Keywords: Pseudomonas aeruginosa; Multidrug-resistant bacteria; bacteriophage; complement system; lung infection; phage therapy.