Standardization of an experimental murine model of invasive pulmonary aspergillosis

Donald C Sheppard1, John R Graybill, Laura K Najvar

  • 1McGill University, Department of Microbiology and Immunology, Montreal, Quebec, Canada. donald.sheppard@mcgill.ca

Insights

Reproducible animal models are crucial for evaluating new invasive aspergillosis treatments. This study confirms a murine model of aerosol infection demonstrates high reproducibility in survival, fungal burden, and treatment efficacy across two independent labs.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Invasive aspergillosis is a serious fungal infection, particularly in immunocompromised patients.
  • Development of new therapeutic agents requires reliable and reproducible preclinical animal models.
  • Previous models for invasive aspergillosis have shown variability, hindering drug development.

Purpose of the Study:

  • To assess the inter- and intra-laboratory reproducibility of a murine model of invasive aspergillosis.
  • To validate the model's suitability for evaluating the efficacy of antifungal agents, specifically liposomal amphotericin B.

Main Methods:

  • A murine model of invasive aspergillosis was established via aerosolized Aspergillus fumigatus.
  • The model was evaluated in two independent laboratories.
  • Key outcomes measured included survival rates, fungal burden over time, and response to liposomal amphotericin B treatment.

Main Results:

  • High levels of intra-laboratory reproducibility were observed for survival, fungal burden, and treatment efficacy.
  • High levels of inter-laboratory reproducibility were also demonstrated across both participating labs.
  • The efficacy of liposomal amphotericin B was consistently evaluated in the model.

Conclusions:

  • The murine model of aerosol infection is a reproducible system for evaluating invasive aspergillosis.
  • This model's reproducibility supports its use in preclinical studies for new antifungal therapies.
  • Consistent results across laboratories enhance confidence in drug efficacy findings.

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