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Burkholderia pseudomallei , the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator.  Burkholderia mallei  is a host-adapted clone of  B. pseudomallei  that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either  Burkholderia  species, and there is concern regarding their use as biological warfare agents given that  B. mallei  has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains  B. pseudomallei  1026b and  B. mallei  ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10 2 , 10 3  and 10 4  organisms were unable to control growth of  B. mallei  in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10 3  and 10 4   B. pseudomallei  cells, animals infected with 10 2  organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections.

Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection by Burkholderia pseudomallei and Burkholderia mallei in Mice