Therapeutic effect of the YH6 phage in a murine hemorrhagic pneumonia model

Res Microbiol. 2015 Oct;166(8):633-43. doi: 10.1016/j.resmic.2015.07.008. Epub 2015 Aug 6.

Abstract

The treatment, in farmed mink, of hemorrhagic pneumonia caused by multidrug-resistant Pseudomonas aeruginosa strains has become increasingly difficult. This study investigated the potential use of phages as a therapy against hemorrhagic pneumonia caused by P. aeruginosa in a murine hemorrhagic pneumonia model. An N4-like phage designated YH6 was isolated using P. aeruginosa strain D9. YH6 is a virulent phage with efficient and broad host lytic activity against P. aeruginosa. No bacterial virulence- or lysogenesis-related ORF is present in the YH6 genome, making it eligible for use in phage therapy. In our murine experiments, a single intranasal administration of YH6 (2 × 10(7) PFU) 2 h after D9 intranasal injections at double minimum lethal dose was sufficient to protect mice against hemorrhagic pneumonia. The bacterial load in the lungs of YH6-protected mice was less than 10(3) CFU/g within 24 h after challenge and ultimately became undetectable, whereas the amount of bacteria in the lung tissue derived from unprotected mice was more than 10(8) CFU/g within 24 h after challenge. In view of its protective efficacy in this murine hemorrhagic pneumonia model, YH6 may serve as an alternative treatment strategy for infections caused by multidrug-resistant P. aeruginosa.

Keywords: Bacteriophage; Mink; Pneumonia model; Pseudomonas aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Bacterial Load
  • Biological Therapy
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial
  • Female
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / therapy*
  • Pseudomonas Infections / immunology
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / therapy*
  • Pseudomonas Phages* / isolation & purification
  • Pseudomonas Phages* / physiology
  • Pseudomonas aeruginosa / pathogenicity*
  • Pseudomonas aeruginosa / virology