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Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa infections: rationale and current status.

Hraiech S, Brégeon F, Rolain JM - Drug Des Devel Ther (2015)

Bottom Line: Among them, bacteriophage-based therapies deserve a focus.One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections.Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia.

View Article: PubMed Central - PubMed

Affiliation: Institut Hospitalo-Universitaire Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France ; Réanimation Médicale - Détresses Respiratoires et Infections Sévères, APHM, CHU Nord, Marseille, France.

ABSTRACT
Pulmonary infections involving Pseudomonas aeruginosa are among the leading causes of the deterioration of the respiratory status of cystic fibrosis (CF) patients. The emergence of multidrug-resistant strains in such populations, favored by iterative antibiotic cures, has led to the urgent need for new therapies. Among them, bacteriophage-based therapies deserve a focus. One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections. Interest in bacteriophages has recently renewed in Western countries, and the in vitro data available suggest that bacteriophage-based therapy may be of significant interest for the treatment of pulmonary infections in CF patients. Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia. Consequently, the aim of this review is, after a brief history, to summarize the evidence concerning bacteriophage efficacy against P. aeruginosa and, more specifically, the in vitro studies, animal models, and clinical trials targeting CF.

No MeSH data available.


Related in: MedlinePlus

Example of Pseudomonas aeruginosa-specific high-titer phage-production protocol. Target strains of P. aeruginosa are incubated separately for 24 hours in the early exponential phase (OD 600 nm =0.1) with a known phage cocktail at a 0.035 multiplicity of infection (= volume of phage suspension/volume of bacterial suspension). After 24 hours, the obtained lysates are centrifuged at 5,000× g for 30 minutes at 4°C. Supernatant is filtered through a 0.2 μm membrane and stored at 4°C.Abbreviations: CFU, colony-forming units; OD, optical density.
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f2-dddt-9-3653: Example of Pseudomonas aeruginosa-specific high-titer phage-production protocol. Target strains of P. aeruginosa are incubated separately for 24 hours in the early exponential phase (OD 600 nm =0.1) with a known phage cocktail at a 0.035 multiplicity of infection (= volume of phage suspension/volume of bacterial suspension). After 24 hours, the obtained lysates are centrifuged at 5,000× g for 30 minutes at 4°C. Supernatant is filtered through a 0.2 μm membrane and stored at 4°C.Abbreviations: CFU, colony-forming units; OD, optical density.

Mentions: Bacteriophages are ubiquitous organisms present in high numbers in the water, soil, and animal-associated ecosystems. Most of the bacteriophages described to date belong to Caudovirales, which is itself composed of Myoviridae, Siphoviridae, and Podoviridae. These bacteriophages share an icosahedral capsid containing a double-stranded linear DNA and a caudal part with structures for adhesion to bacteria. Lytic phages lead to bacterial death and are weakly implicated in horizontal gene transfer (responsible for antibiotic-resistance gene transfer). This is contrary to the lysogenic bacteriophages11 that can integrate into the bacterial genome as prophages and be responsible for virulence factor transfer. Easy to extract, phage isolation is rapid and cost-effective so that any bacterial infection could, in theory, be controlled by bacteriophage-based therapy (Figures 1 and 2). However, the efficacy of the isolated bacteriophages needs verification prior to use, and results obtained in vitro cannot determine effectiveness in vivo, especially when the lung is concerned.


Bacteriophage-based therapy in cystic fibrosis-associated Pseudomonas aeruginosa infections: rationale and current status.

Hraiech S, Brégeon F, Rolain JM - Drug Des Devel Ther (2015)

Example of Pseudomonas aeruginosa-specific high-titer phage-production protocol. Target strains of P. aeruginosa are incubated separately for 24 hours in the early exponential phase (OD 600 nm =0.1) with a known phage cocktail at a 0.035 multiplicity of infection (= volume of phage suspension/volume of bacterial suspension). After 24 hours, the obtained lysates are centrifuged at 5,000× g for 30 minutes at 4°C. Supernatant is filtered through a 0.2 μm membrane and stored at 4°C.Abbreviations: CFU, colony-forming units; OD, optical density.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4509528&req=5

f2-dddt-9-3653: Example of Pseudomonas aeruginosa-specific high-titer phage-production protocol. Target strains of P. aeruginosa are incubated separately for 24 hours in the early exponential phase (OD 600 nm =0.1) with a known phage cocktail at a 0.035 multiplicity of infection (= volume of phage suspension/volume of bacterial suspension). After 24 hours, the obtained lysates are centrifuged at 5,000× g for 30 minutes at 4°C. Supernatant is filtered through a 0.2 μm membrane and stored at 4°C.Abbreviations: CFU, colony-forming units; OD, optical density.
Mentions: Bacteriophages are ubiquitous organisms present in high numbers in the water, soil, and animal-associated ecosystems. Most of the bacteriophages described to date belong to Caudovirales, which is itself composed of Myoviridae, Siphoviridae, and Podoviridae. These bacteriophages share an icosahedral capsid containing a double-stranded linear DNA and a caudal part with structures for adhesion to bacteria. Lytic phages lead to bacterial death and are weakly implicated in horizontal gene transfer (responsible for antibiotic-resistance gene transfer). This is contrary to the lysogenic bacteriophages11 that can integrate into the bacterial genome as prophages and be responsible for virulence factor transfer. Easy to extract, phage isolation is rapid and cost-effective so that any bacterial infection could, in theory, be controlled by bacteriophage-based therapy (Figures 1 and 2). However, the efficacy of the isolated bacteriophages needs verification prior to use, and results obtained in vitro cannot determine effectiveness in vivo, especially when the lung is concerned.

Bottom Line: Among them, bacteriophage-based therapies deserve a focus.One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections.Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia.

View Article: PubMed Central - PubMed

Affiliation: Institut Hospitalo-Universitaire Méditerranée Infection, URMITE CNRS IRD INSERM UMR 7278, Marseille, France ; Réanimation Médicale - Détresses Respiratoires et Infections Sévères, APHM, CHU Nord, Marseille, France.

ABSTRACT
Pulmonary infections involving Pseudomonas aeruginosa are among the leading causes of the deterioration of the respiratory status of cystic fibrosis (CF) patients. The emergence of multidrug-resistant strains in such populations, favored by iterative antibiotic cures, has led to the urgent need for new therapies. Among them, bacteriophage-based therapies deserve a focus. One century of empiric use in the ex-USSR countries suggests that bacteriophages may have beneficial effects against a large range of bacterial infections. Interest in bacteriophages has recently renewed in Western countries, and the in vitro data available suggest that bacteriophage-based therapy may be of significant interest for the treatment of pulmonary infections in CF patients. Although the clinical data concerning this specific population are relatively scarce, the beginning of the first large randomized study evaluating bacteriophage-based therapy in burn infections suggests that the time has come to assess the effectiveness of this new therapy in CF P. aeruginosa pneumonia. Consequently, the aim of this review is, after a brief history, to summarize the evidence concerning bacteriophage efficacy against P. aeruginosa and, more specifically, the in vitro studies, animal models, and clinical trials targeting CF.

No MeSH data available.


Related in: MedlinePlus