Bacteriophages MR299-2 and NH-4 Can Eliminate Pseudomonas aeruginosa

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MBio. 2012 Mar 6;3(2). pii: e00029-12. doi: 10.1128/mBio.00029-12.
Print 2012.
Bacteriophages MR299-2 and NH-4 Can Eliminate Pseudomonas aeruginosa
in the Murine Lung and on Cystic Fibrosis Lung Airway Cells.
Alemayehu D, Casey PG, McAuliffe O, Guinane CM, Martin JG, Shanahan F,
Coffey A, Ross RP, Hill C.
Source
TEAGASC Food Research Centre, Moorepark, Fermoy, Co. Cork, Ireland.
Abstract
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 (NH-4) and a podovirus
(MR299-2). 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 × 10(7) to 2 × 10(7) 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.