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The pathophysiology of inhalational brucellosis in BALB/c mice
Lisa N Henning1, Karen T Gillum, David A Fisher
1Battelle, 505 King Avenue Columbus, Ohio 43201, USA. henningl@battelle.org
Abstract:
To characterize the clinical presentation and pathophysiology of inhalational brucellosis, Balb/c mice were challenged with Brucella melitensis 16M in a nose-only aerosol exposure chamber. A low dose of 1000 cfu/animal of B. melitensis resulted in 45% of mice with tissue burdens eight weeks post-challenge. The natural history of brucellosis in mice challenged by higher aerosol doses was examined by serial euthanizing mice over an eight week period. Higher challenge doses of 1.00E+05 and 5.00E+05 cfu resulted in positive blood cultures 14 days post-challenge and bacterial burdens were observed in the lung, liver and/or spleens 14 days post-challenge. In addition, the progression of brucellosis was similar between mice challenged by the intranasal and aerosol routes. The results from this study support the use of the Balb/c aerosol nose-only brucellosis mouse model for the evaluation of therapeutics against inhalational brucellosis.
Insights
This study characterizes inhalational brucellosis in mice, finding that aerosol exposure effectively establishes infection. The Balb/c mouse model is suitable for evaluating new brucellosis therapeutics.
Area of Science:
- Microbiology
- Infectious Diseases
- Immunology
Background:
- Brucellosis is a zoonotic disease with significant public health implications.
- Inhalational brucellosis presents unique challenges for diagnosis and treatment.
- Animal models are crucial for understanding disease pathogenesis and testing interventions.
Purpose of the Study:
- To characterize the clinical presentation and pathophysiology of inhalational brucellosis.
- To establish and validate a Balb/c mouse model for inhalational brucellosis.
- To assess the efficacy of the model for evaluating therapeutics.
Main Methods:
- Balb/c mice were challenged with Brucella melitensis 16M via nose-only aerosol exposure.
- Low and high doses of bacteria were used to determine dose-dependent effects.
- Mice were monitored over an eight-week period, with serial euthanization for tissue burden analysis and blood cultures.
Main Results:
- A low dose (1000 cfu/animal) resulted in tissue burdens in 45% of mice eight weeks post-challenge.
- Higher doses (1.00E+05 and 5.00E+05 cfu) led to positive blood cultures and bacterial burdens in organs by 14 days post-challenge.
- Disease progression was comparable between intranasal and aerosol challenge routes.
Conclusions:
- The Balb/c mouse model effectively mimics inhalational brucellosis.
- This model is suitable for evaluating the efficacy of therapeutics against inhalational brucellosis.
- Further research can utilize this model to develop novel treatment strategies.
