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Effectiveness of bacteriophages in the sputum of cystic fibrosis patients

Authors :
Raphaël Chiron
Laurent Debarbieux
Frédérique Carrié
Nicolas Molinari
Isabelle Sermet
Isabelle Vachier
Jean-Paul Pirnay
Emilie Saussereau
Nicolas Dufour
Benoit Godbert
Daniel De Vos
Debarbieux, Laurent
Cellule Pasteur UPMC
Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)
Biologie Moléculaire du Gène chez les Extrêmophiles (BMGE)
Institut Pasteur [Paris] (IP)
Département des Maladies Respiratoires [Montpellier]
Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve
Service de Pneumologie [CHRU Nancy]
Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Centre de recherche Croissance et signalisation (UMR_S 845)
Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Cellule Pasteur
Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité
Laboratory for Molecular and Cellular Technology
Queen Astrid Military Hospital [Brussels]
PHAGESPOIRS
Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie (MISTEA)
Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)
This work was supported by Vaincre la Mucoviscidose, the French Cystic Fibrosis Foundation [RC20120600714/1/1/141], and Programme Transversal de Recherches [417] from Institut Pasteur and Assistance Publique Hôpitaux de Paris.
Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]
Institut Pasteur [Paris]
Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)
Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)
PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7)
Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)
Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut Pasteur [Paris]
Biologie Moléculaire du Gène chez les Extrêmophiles ( BMGE )
Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Arnaud de Villeneuve
Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy )
Centre de recherche Croissance et signalisation ( UMR_S 845 )
Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité
Mathématiques, Informatique et STatistique pour l'Environnement et l'Agronomie ( MISTEA )
Institut National de la Recherche Agronomique ( INRA ) -Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro )
Source :
Clinical Microbiology and Infection, Clinical Microbiology and Infection, 2014, 20 (12), pp.O983-90. ⟨10.1111/1469-0691.12712⟩, Clinical Microbiology and Infection, Elsevier for the European Society of Clinical Microbiology and Infectious Diseases, 2014, 20 (12), pp.O983-90. ⟨10.1111/1469-0691.12712⟩, Clinical Microbiology and Infection, Elsevier for the European Society of Clinical Microbiology and Infectious Diseases, 2014, 20 (12), pp.O983-90. 〈10.1111/1469-0691.12712〉
Publication Year :
2014
Publisher :
Elsevier BV, 2014.

Abstract

International audience; Bacteriophages have been shown to be effective for treating acute infections of the respiratory tract caused by antibiotic-resistant bacteria in animal models, but no evidence has yet been presented of their activity against pathogens in complex biological samples from chronically infected patients. We assessed the efficacy of a cocktail of ten bacteriophages infecting Pseudomonas aeruginosa following its addition to 58 sputum samples from cystic fibrosis (CF) patients collected at three different hospitals. Ten samples that did not contain P. aeruginosa were not analysed further. In the remaining 48 samples, the addition of bacteriophages led to a significant decrease in the levels of P. aeruginosa strains, as shown by comparison with controls, taking two variables (time and bacteriophages) into account (p = 0.024). In 45.8% of these samples, this decrease was accompanied by an increase in the number of bacteriophages. We also tested each of the ten bacteriophages individually against 20 colonies from each of these 48 samples and detected bacteriophage-susceptible bacteria in 64.6% of the samples. An analysis of the clinical data revealed no correlation between patient age, sex, duration of P. aeruginosa colonization, antibiotic treatment, FEV1 (forced expiratory volume in the first second) and the efficacy of bacteriophages. The demonstration that bacteriophages infect their bacterial hosts in the sputum environment, regardless of the clinical characteristics of the patients, represents a major step towards the development of bacteriophage therapy to treat chronic lung infections.

Subjects

Subjects :
Male
Time Factors
Cystic Fibrosis
medicine.medical_treatment
Antibiotics
pulmonary infection
[ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
medicine.disease_cause
MESH: Bacterial Load
Cystic fibrosis
MESH : Cross-Sectional Studies
MESH: Sputum
MESH : Female
MESH: Microbial Viability
MESH: Middle Aged
biology
MESH: Pseudomonas Infections
General Medicine
MESH : Adult
MESH : Pseudomonas aeruginosa
Middle Aged
MESH : Pseudomonas Infections
3. Good health
Biological Therapy
Chronic infection
medicine.anatomical_structure
Infectious Diseases
MESH: Young Adult
Pseudomonas aeruginosa
MESH: Pseudomonas aeruginosa
Female
MESH : Bacterial Load
medicine.symptom
Pseudomonas Phages
MESH : Time Factors
Adult
Microbiology (medical)
phage therapy
Phage therapy
Adolescent
MESH: Cystic Fibrosis
medicine.drug_class
MESH : Male
MESH : Young Adult
MESH: Pseudomonas Phages
Microbiology
Young Adult
MESH: Cross-Sectional Studies
MESH : Adolescent
MESH : Cystic Fibrosis
medicine
Humans
MESH : Middle Aged
Pseudomonas Infections
MESH: Adolescent
Microbial Viability
MESH: Humans
MESH : Humans
MESH: Time Factors
MESH : Microbial Viability
Sputum
MESH: Adult
medicine.disease
biology.organism_classification
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Bacterial Load
MESH: Male
Cross-Sectional Studies
MESH : Pseudomonas Phages
MESH : Sputum
[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
MESH: Biological Therapy
MESH: Female
MESH : Biological Therapy
Bacteria
Respiratory tract

Details

ISSN :
1198743X and 14690691
Volume :
20
Issue :
12
Database :
OpenAIRE
Journal :
Clinical Microbiology and Infection
Accession number :
edsair.doi.dedup.....11356e76a9aa304ae12707ee67886d81
Full Text :
https://doi.org/10.1111/1469-0691.12712