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Long Term Chronic Pseudomonas aeruginosa Airway Infection in Mice
Published on: March 17, 2014
Biologically Relevant Murine Models of Chronic Pseudomonas aeruginosa Respiratory Infection
Aoife M Rodgers1, Jaime Lindsay1, Avril Monahan1
1Wellcome-Wolfson Institute of Experimental Medicine, Queen's University Belfast, Belfast BT7 1NN, UK.
Abstract:
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described: a clinical isolate infection model, utilising isolates obtained from patients with CF; an incomplete antibiotic clearance model, leading to bacterial bounce-back; and the establishment of chronic infection; and an adapted water bottle chronic infection model. These models circumvent the requirement for a surgical procedure and, importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.
Insights
New mouse models for chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients avoid surgery and use clinical isolates. These models aid research into host factors and new antimicrobial treatments.
Area of Science:
- Microbiology
- Infectious Diseases
- Pulmonary Medicine
Background:
- Pseudomonas aeruginosa (P. aeruginosa) is a major cause of lung infections in cystic fibrosis (CF) patients.
- Chronic P. aeruginosa infections lead to significant illness and death, often evading host defenses.
- Existing mouse models, like the bead agar model, have limitations including surgical requirements and high mortality.
Purpose of the Study:
- To develop novel and adapted, biologically relevant mouse models for studying chronic P. aeruginosa lung infections.
- To overcome the limitations of existing models, such as surgical procedures and high mortality rates.
- To facilitate research into host-pathogen interactions and novel antimicrobial therapies for chronic P. aeruginosa infections.
Main Methods:
- Three non-surgical models were developed: a clinical isolate infection model, an incomplete antibiotic clearance model, and an adapted water bottle model.
- These models utilize clinical P. aeruginosa isolates obtained directly from CF patients.
- Chronic infection was successfully induced in both wild-type mice and the transgenic βENaC murine model of CF.
Main Results:
- The developed models successfully established chronic P. aeruginosa lung infections without requiring surgical intervention.
- Clinical isolates of P. aeruginosa were effectively used to induce infection in wild-type mice.
- Chronic infection was also confirmed in the transgenic βENaC murine model, relevant to CF.
Conclusions:
- The novel and adapted models provide viable, less invasive alternatives for studying chronic P. aeruginosa respiratory infections.
- These models are suitable for investigating host and microbial factors contributing to chronic infection.
- The models will aid in evaluating the efficacy of new antimicrobial treatments against chronic P. aeruginosa lung infections in relevant mouse models.

