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Experimental aerogenic Burkholderia mallei (glanders) infection in the BALB/c mouse
M Stephen Lever1, Michelle Nelson1, Philip I Ireland1
1DSTL Biomedical Sciences1 and CAMR2, Porton Down, Salisbury, Wiltshire, UK.
Abstract:
The object of this study was to develop and characterize experimental Burkholderia mallei aerosol infection in BALB/c mice. Sixty-five mice were infected with 5000 [approx. 2.5 median lethal doses (MLD)] B. mallei strain ATCC 23344(T) bacteria by the aerosol route. Bacterial counts within lung, liver, spleen, brain, kidney and blood over 14 days were determined and histopathological and immunocytochemical profiles were assessed. Mortality due to B. mallei infection occurred between days 4 and 10 post-infection. Bacterial numbers were consistently higher in the lungs than in other tissues, reaching a maximum of approximately 1.0 x 10(6) c.f.u. ml(-1) at 5 days post-infection. Bacterial counts in liver and spleen tissue remained approximately equal, reaching a maximum of approximately 1.0 x 10(4) c.f.u. ml(-1) at day 4 post-infection. By day 14 post-infection, bacterial counts were in the range 1.0 x 10(3)-1.0 x 10(4) c.f.u. ml(-1) for all tissues. Infection of the lungs by B. mallei resulted in foci of acute inflammation and necrosis. As infection progressed, the inflammatory process became subacute or chronic; this was associated with the development of extensive consolidation. Lesions in liver and spleen tissue were typical of those that might be expected in bacteraemia or bacterial toxaemia. These results suggest that the BALB/c mouse is susceptible to B. mallei when delivered by the aerosol route and that this represents a model system of acute human glanders that is suitable for research into the pathogenesis of and vaccines against this disease.
Insights
This study developed an experimental aerosol infection model using Burkholderia mallei in BALB/c mice. The model effectively mimics acute human glanders, proving useful for researching disease pathogenesis and vaccine development.
Area of Science:
- Microbiology
- Infectious Diseases
- Animal Models
Background:
- Burkholderia mallei causes glanders, a zoonotic disease with significant public health implications.
- Developing reliable animal models is crucial for understanding glanders pathogenesis and evaluating countermeasures.
Purpose of the Study:
- To establish and characterize an experimental aerosol infection model of Burkholderia mallei in BALB/c mice.
- To assess the suitability of this model for studying glanders and developing vaccines.
Main Methods:
- Sixty-five BALB/c mice were infected via aerosol with B. mallei strain ATCC 23344(T).
- Bacterial loads were quantified in various tissues (lung, liver, spleen, brain, kidney, blood) over 14 days.
- Histopathological and immunocytochemical analyses were performed to assess tissue damage and inflammation.
Main Results:
- Mortality occurred between days 4 and 10 post-infection, with bacterial counts highest in the lungs.
- Bacterial dissemination to liver and spleen was observed, with peak counts around day 4.
- Lung infection led to acute inflammation, necrosis, and consolidation, progressing to subacute/chronic stages.
Conclusions:
- BALB/c mice are susceptible to aerosolized B. mallei, establishing a relevant model for acute glanders.
- This model is suitable for research into glanders pathogenesis and the development of effective vaccines.
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