Experimental aerogenic Burkholderia mallei (glanders) infection in the BALB/c mouse

DSTL Biomedical Sciences 1 and CAMR 2 , Porton Down, Salisbury, Wiltshire, UK Correspondence M. Stephen Lever mslever{at}dstl.gov.uk Received January 10, 2003 Accepted August 11, 2003 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. Abbreviations: H&E, haematoxylin and eosin; MLD, median lethal dose.