Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice.
Authors: Lafontaine Eric R, Zimmerman Shawn M, Shaffer Teresa L, Michel Frank, Gao Xiudan, Hogan Robert J
Journal: PloS one
Summary
Burkholderia mallei (causative agent of equine glanders) and B. pseudomallei (melioidosis) are environmentally persistent pathogens with significant zoonotic potential, yet researchers have lacked suitable animal models to investigate infection mechanisms and develop therapeutic countermeasures, particularly for the inhalation route most commonly encountered in natural disease. Lafontaine and colleagues established a reproducible aerosol delivery system using BALB/c mice and intratracheal inoculation with both Burkholderia species to characterise dose-dependent pathogenesis, bacterial dissemination patterns, and immune responses. Mice exposed to B. mallei (at 10², 10³, and 10⁴ colony-forming units) developed progressive pulmonary infection with rapid splenic dissemination regardless of inoculum size, whereas B. pseudomallei-infected animals showed dose-dependent outcomes—those receiving 10² organisms controlled infection locally, whilst higher doses (10³-10⁴) mirrored the aggressive B. mallei phenotype with widespread systemic infection. Surviving animals mounted serological responses targeting antigens implicated in human immune defence, validating this model's translational relevance. For equine practitioners, these findings underscore the aggressive nature of B. mallei infection, the critical importance of early diagnosis before bacteraemia develops, and the potential value of emerging immunological targets for future vaccine or therapeutic development should prevention strategies become available.
Read the full abstract on PubMed
Practical Takeaways
- •This is fundamental research on pathogenic bacteria in rodent models — not directly applicable to equine clinical practice or management
- •B. mallei (glanders) is an important equine zoonotic disease with high fatality rates; however, this paper studies mouse models, not horses
- •While relevant to understanding glanders epidemiology and vaccine development research, this work does not provide clinical guidance for diagnosis, treatment, or biosecurity in equine settings
Key Findings
- •B. mallei rapidly disseminated from lungs to spleen and caused fatal infection at all tested doses (10² to 10⁴ organisms) in mice
- •B. pseudomallei showed dose-dependent infection patterns, with 10² organisms controlled by immune response but 10³-10⁴ organisms causing dissemination
- •Surviving mice produced antibodies against B. pseudomallei antigens consistent with human immune responses to infection
- •Hand-held aerosolizer method successfully established reproducible mouse model for studying aerosol transmission of both Burkholderia species