Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells

ABSTRACT Pseudomonas aeruginosa is a common cause of infection in the lungs of patients with cystic fibrosis (CF). In addition, biofilm formation and antibiotic resistance of Pseudomonas are major problems that can complicate antibiotic therapy. We evaluated the efficacy of using bacteriophages to k...

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Autores principales:	Debebe Alemayehu, Pat G. Casey, Olivia McAuliffe, Caitriona M. Guinane, James G. Martin, Fergus Shanahan, Aidan Coffey, R. Paul Ross, Colin Hill
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/07c5b41765604bca8ec708c477a6fa8a
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spelling	oai:doaj.org-article:07c5b41765604bca8ec708c477a6fa8a2021-11-15T15:39:09ZBacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells10.1128/mBio.00029-122150-7511https://doaj.org/article/07c5b41765604bca8ec708c477a6fa8a2012-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00029-12https://doaj.org/toc/2150-7511ABSTRACT Pseudomonas aeruginosa is a common cause of infection in the lungs of patients with cystic fibrosis (CF). In addition, biofilm formation and antibiotic resistance of Pseudomonas are major problems that can complicate antibiotic therapy. We evaluated the efficacy of using bacteriophages to kill the pathogen in both biofilms and in the murine lung. We isolated and characterized two phages from a local wastewater treatment plant, a myovirus (ϕNH-4) and a podovirus (ϕMR299-2). Both phages were active against clinical isolates of P. aeruginosa. Together, the two phages killed all 9 clinical isolate strains tested, including both mucoid and nonmucoid strains. An equal mixture of the two phages was effective in killing P. aeruginosa NH57388A (mucoid) and P. aeruginosa MR299 (nonmucoid) strains when growing as a biofilm on a cystic fibrosis bronchial epithelial CFBE41o- cell line. Phage titers increased almost 100-fold over a 24-h period, confirming replication of the phage. Furthermore, the phage mix was also effective in killing the pathogen in murine lungs containing 1 × 107 to 2 × 107 P. aeruginosa. Pseudomonas was effectively cleared (reduced by a magnitude of at least 3 to 4 log units) from murine lungs in 6 h. Our study demonstrates the efficacy of these two phages in killing clinical Pseudomonas isolates in the murine lung or as a biofilm on a pulmonary cell line and supports the growing interest in using phage therapy for the control and treatment of multidrug-resistant Pseudomonas lung infections in CF patients. IMPORTANCE Given the rise in antibiotic resistance, nonantibiotic therapies are required for the treatment of infection. This is particularly true for the treatment of Pseudomonas infection in patients with cystic fibrosis. We have identified two bacterial viruses (bacteriophages) that can kill Pseudomonas growing on human lung cells and in an animal model of lung infection. The use of bacteriophages is particularly appropriate because the killing agent can replicate on the target cell, generating fresh copies of the bacteriophage. Thus, in the presence of a target, the killing agent multiplies. By using two bacteriophages we can reduce the risk of resistant colonies developing at the site of infection. Bacteriophage therapy is an exciting field, and this study represents an important demonstration of efficacy in validated infection models.Debebe AlemayehuPat G. CaseyOlivia McAuliffeCaitriona M. GuinaneJames G. MartinFergus ShanahanAidan CoffeyR. Paul RossColin HillAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 2 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Debebe Alemayehu Pat G. Casey Olivia McAuliffe Caitriona M. Guinane James G. Martin Fergus Shanahan Aidan Coffey R. Paul Ross Colin Hill Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells
description	ABSTRACT Pseudomonas aeruginosa is a common cause of infection in the lungs of patients with cystic fibrosis (CF). In addition, biofilm formation and antibiotic resistance of Pseudomonas are major problems that can complicate antibiotic therapy. We evaluated the efficacy of using bacteriophages to kill the pathogen in both biofilms and in the murine lung. We isolated and characterized two phages from a local wastewater treatment plant, a myovirus (ϕNH-4) and a podovirus (ϕMR299-2). Both phages were active against clinical isolates of P. aeruginosa. Together, the two phages killed all 9 clinical isolate strains tested, including both mucoid and nonmucoid strains. An equal mixture of the two phages was effective in killing P. aeruginosa NH57388A (mucoid) and P. aeruginosa MR299 (nonmucoid) strains when growing as a biofilm on a cystic fibrosis bronchial epithelial CFBE41o- cell line. Phage titers increased almost 100-fold over a 24-h period, confirming replication of the phage. Furthermore, the phage mix was also effective in killing the pathogen in murine lungs containing 1 × 107 to 2 × 107 P. aeruginosa. Pseudomonas was effectively cleared (reduced by a magnitude of at least 3 to 4 log units) from murine lungs in 6 h. Our study demonstrates the efficacy of these two phages in killing clinical Pseudomonas isolates in the murine lung or as a biofilm on a pulmonary cell line and supports the growing interest in using phage therapy for the control and treatment of multidrug-resistant Pseudomonas lung infections in CF patients. IMPORTANCE Given the rise in antibiotic resistance, nonantibiotic therapies are required for the treatment of infection. This is particularly true for the treatment of Pseudomonas infection in patients with cystic fibrosis. We have identified two bacterial viruses (bacteriophages) that can kill Pseudomonas growing on human lung cells and in an animal model of lung infection. The use of bacteriophages is particularly appropriate because the killing agent can replicate on the target cell, generating fresh copies of the bacteriophage. Thus, in the presence of a target, the killing agent multiplies. By using two bacteriophages we can reduce the risk of resistant colonies developing at the site of infection. Bacteriophage therapy is an exciting field, and this study represents an important demonstration of efficacy in validated infection models.
format	article
author	Debebe Alemayehu Pat G. Casey Olivia McAuliffe Caitriona M. Guinane James G. Martin Fergus Shanahan Aidan Coffey R. Paul Ross Colin Hill
author_facet	Debebe Alemayehu Pat G. Casey Olivia McAuliffe Caitriona M. Guinane James G. Martin Fergus Shanahan Aidan Coffey R. Paul Ross Colin Hill
author_sort	Debebe Alemayehu
title	Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells
title_short	Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells
title_full	Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells
title_fullStr	Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells
title_full_unstemmed	Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells
title_sort	bacteriophages ϕmr299-2 and ϕnh-4 can eliminate <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> in the murine lung and on cystic fibrosis lung airway cells
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/07c5b41765604bca8ec708c477a6fa8a
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Bacteriophages ϕMR299-2 and ϕNH-4 Can Eliminate <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> in the Murine Lung and on Cystic Fibrosis Lung Airway Cells

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