title: 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.
authors.affiliation: Molecular Biology of the Gene in Extremophiles Unit, Department of Microbiology, Institut Pasteur, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Morello
authors.forename: Emilie
authors.initials: E
authors.lastname: Saussereau
authors.forename: Damien
authors.initials: D
authors.lastname: Maura
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
authors.forename: Laurent
authors.initials: L
authors.lastname: Debarbieux
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001435:Bacteriophages / Q000472:pathogenicity / Q000502:physiology*; D003550:Cystic Fibrosis / Q000382:microbiology / Q000517:prevention & control* / Q000628:therapy*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity* / Q000821:virology*; D013045:Species Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D014764:Viral Proteins