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Experimental acute respiratory Burkholderia pseudomallei infection in BALB/c mice
Mark S Lever1, Michelle Nelson, Anthony J Stagg
1Biomedical Sciences, Defence Science and Technology Laboratory (Dstl), Porton Down, Salisbury, UK. mslever@dstl.gov.uk
Abstract:
Burkholderia pseudomallei is the causative agent of melioidosis, which is considered a potential deliberate release agent. The objective of this study was to establish and characterise a relevant, acute respiratory Burkholderia pseudomallei infection in BALB/c mice. Mice were infected with 100 B. pseudomallei strain BRI bacteria by the aerosol route (approximately 20 median lethal doses). Bacterial counts within lung, liver, spleen, brain, kidney and blood over 5 days were determined and histopathological and immunocytochemical profiles were assessed. Bacterial numbers in the lungs reached approximately 10(8) cfu/ml at day 5 post-infection. Bacterial numbers in other tissues were lower, reaching between 10(3) and 10(5) cfu/ml at day 4. Blood counts remained relatively constant at approximately 1.0 x 10(2) cfu/ml. Foci of acute inflammation and necrosis were seen within lungs, liver and spleen. These results suggest that the BALB/c mouse is highly susceptible to B. pseudomallei by the aerosol route and represents a relevant model system of acute human melioidosis.
Insights
This study establishes a mouse model for acute melioidosis caused by Burkholderia pseudomallei. BALB/c mice exposed to aerosolized bacteria developed severe lung infections, demonstrating susceptibility and relevance for studying this potential biothreat agent.
Area of Science:
- Microbiology
- Pathogen Research
- Infectious Diseases
Background:
- Melioidosis is caused by Burkholderia pseudomallei, a bacterium recognized as a potential bioweapon.
- Developing an effective animal model is crucial for understanding melioidosis pathogenesis and treatment.
Purpose of the Study:
- To establish and characterize an acute respiratory infection model of Burkholderia pseudomallei in BALB/c mice.
- To assess the susceptibility of BALB/c mice to aerosolized B. pseudomallei.
Main Methods:
- BALB/c mice were infected via aerosol with 100 B. pseudomallei strain BRI bacteria (approx. 20 median lethal doses).
- Bacterial loads in lungs, liver, spleen, brain, kidney, and blood were quantified over 5 days.
- Histopathological and immunocytochemical analyses were performed.
Main Results:
- Rapid bacterial proliferation in lungs, reaching approximately 10(8) cfu/ml by day 5.
- Significant bacterial presence in other organs (10^3–10^5 cfu/ml) by day 4.
- Acute inflammation and necrosis observed in lungs, liver, and spleen.
Conclusions:
- BALB/c mice are highly susceptible to aerosolized B. pseudomallei.
- This model accurately reflects acute human melioidosis, aiding further research.
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