Type

Journal Article

Authors

Colin Hill
R Paul Ross
Aidan Coffey
Fergus Shanahan
James G Martin
Caitriona M Guinane
Olivia McAuliffe
Pat G. Casey
Debebe Alemayehu

Subjects

Microbiology

Topics
pseudomonas aeruginosa animals disease models animal epithelial cells complications microbiology myoviridae biological therapy lung sequence analysis dna bronchopneumonia growth development cell line mice virology isolation purification therapy humans bacterial load water microbiology cystic fibrosis chemistry pseudomonas infections female genetics molecular sequence data podoviridae pseudomonas phages mice inbred balb c dna viral

Bacteriophages φMR299-2 and φNH-4 can eliminate Pseudomonas aeruginosa in the murine lung and on cystic fibrosis lung airway cells. (2012)

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 × 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.
Collections Ireland -> Teagasc -> PubMed

Full list of authors on original publication

Colin Hill, R Paul Ross, Aidan Coffey, Fergus Shanahan, James G Martin, Caitriona M Guinane, Olivia McAuliffe, Pat G. Casey, Debebe Alemayehu

Experts in our system

1
Colin Hill
University College Cork
Total Publications: 351
 
2
R Paul Ross
Teagasc
Total Publications: 441
 
3
Aidan Coffey
Teagasc
Total Publications: 63
 
4
Fergus Shanahan
University College Cork
Total Publications: 237
 
5
James G. Martin
University College Cork
Total Publications: 5
 
6
Caitriona M Guinane
Teagasc
Total Publications: 35
 
7
Olivia McAuliffe
Teagasc
Total Publications: 64
 
8
Pat G. Casey
University College Cork
Total Publications: 40