Long term chronic Pseudomonas aeruginosa airway infection in mice

Marcella Facchini1, Ida De Fino1, Camilla Riva1

  • 1Infections and Cystic Fibrosis Unit, Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute; Italian Cystic Fibrosis Research Foundation.

Insights

This study introduces an improved mouse model for chronic Pseudomonas aeruginosa lung infection, crucial for cystic fibrosis research. The method ensures persistent infection, closely mimicking human disease for better therapeutic evaluation.

Area of Science:

  • Pulmonary Medicine
  • Infectious Diseases
  • Animal Models

Background:

  • Cystic fibrosis (CF) research relies on mouse models for chronic airway infection.
  • Existing models struggle with low bacterial burden and short-term infection duration.
  • Long-term in vivo studies of Pseudomonas aeruginosa infection in mice are limited.

Purpose of the Study:

  • To develop an efficient method for achieving long-term chronic Pseudomonas aeruginosa infection in mice.
  • To establish a murine model that accurately reflects human cystic fibrosis lung disease progression.
  • To enable robust studies on pathogenesis and therapeutic interventions for chronic lung infections.

Main Methods:

  • Embedding Pseudomonas aeruginosa clinical strains in agar-beads in vitro.
  • Intratracheal instillation of agar-beads into C57Bl/6NCrl mice.
  • Utilizing the P. aeruginosa RP73 clinical strain for enhanced infection persistence and severity.

Main Results:

  • Achieved efficient and sustained long-term chronic lung infection in mice, persisting over three months.
  • Observed significant weight loss, mortality, and inflammatory responses.
  • The P. aeruginosa RP73 strain demonstrated superior performance over the PAO1 strain, yielding more severe lesions and higher chronic infection rates.
  • Murine lung pathology closely resembled advanced chronic pulmonary disease in human CF patients.

Conclusions:

  • The developed method provides a robust mouse model for long-term chronic Pseudomonas aeruginosa lung infection.
  • This model closely mimics human cystic fibrosis lung disease, offering a valuable tool for pathogenesis research.
  • The model is suitable for evaluating novel therapeutic strategies against chronic P. aeruginosa infections in CF.