Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention

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 bacteria...

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Veröffentlicht in:PloS one 2011-02, Vol.6 (2), p.e16963-e16963
Hauptverfasser: Morello, Eric, Saussereau, Emilie, Maura, Damien, Huerre, Michel, Touqui, Lhousseine, Debarbieux, Laurent
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Saussereau, Emilie
Maura, Damien
Huerre, Michel
Touqui, Lhousseine
Debarbieux, Laurent
description 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.
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subjects Alveoli
Amino Acid Sequence
Analysis
Animals
Antibiotics
Antigens
Bacteria
Bacterial diseases
Bacterial infections
Bacteriophages - pathogenicity
Bacteriophages - physiology
Biocompatibility
Biofilms
Biology
Bronchus
Burkholderia cenocepacia
Catheters
Computational fluid dynamics
Correlation analysis
Cystic fibrosis
Cystic Fibrosis - microbiology
Cystic Fibrosis - prevention & control
Cystic Fibrosis - therapy
Cytokines
Cytotoxicity
Drug Resistance, Multiple, Bacterial
Environmental monitoring
Enzymes
Epidemiology
Health aspects
Histology
Host range
Humans
Immunohistochemistry
Infection
Infections
Inflammation
Lung - microbiology
Lungs
Male
Medicine
Mice
Microscopy
Molecular biology
Molecular Sequence Data
Multidrug resistance
Optimization
Phages
Pneumonia
Prevention
Preventive medicine
Pseudomonas aeruginosa
Pseudomonas aeruginosa - pathogenicity
Pseudomonas aeruginosa - virology
Species Specificity
Strains (organisms)
Survival
Therapeutic applications
Therapy
Toxicity
Viral Proteins - chemistry
Viral Proteins - metabolism
Viruses
title Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention
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