Pulmonary Bacteriophage Therapy on Pseudomonas aeruginosa Cystic Fibrosis Strains: First Steps Towards Treatment and Prevention

Abstract

Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy—the use of specific viruses that infect bacteria—is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose) administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose) resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.

Characterization and Detection of Endolysin Gene from Three Acinetobacter baumannii Bacteriophages Isolated from Sewage Water

“…Phage therapy is one potential candidate for the treatment of multidrug resistant bacteria [5]. Clinical trials of bacteriophages and their derivatives as potential alternative agents for controlling multi drug resistance infection have been described in various bacterial pathogens [6][7][8][9]. Bacteriophages are able to replicate in the host cell and produce endolysin to lyse the host cell.…”

Outer Membrane Proteins Ail and OmpF of Yersinia pestis Are Involved in the Adsorption of T7-Related Bacteriophage Yep-phi

“…Thus, there is an urgent need for improved treatments and detection methods. Phage therapy has been proposed since their discovery in the early 20th century (5). However, the advent of antibiotics led to this therapeutic approach being largely abandoned (5,6).…”

“…However, the advent of antibiotics led to this therapeutic approach being largely abandoned (5,6). Nevertheless, renewed interest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens (7,8), with several phages shown to be effective in treating various bacterial infections (5,9).…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Phage-Related Therapy

“…The curative treatment of one single dose 2 hours after bacterial infection allowed over 95% survival and preventive treatment with single dose 4 days before infection resulted in 100% survival whereas untreated mice all died within 2 days after infection [64].…”