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.

PubMed

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.

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