Burkholderia Background

Burkholderia pseudomallei is a Gram-negative bacterium residing in the water and wet soils of endemic areas bordering the equator, particularly Southeast Asia and Northern Australia. The genome of B. pseudomallei consists of two chromosomes of 4.1 and 3.2 Mbp. Burkholderia mallei is a non-motile, host-adapted clone of B. pseudomallei that does not persist outside of its equine host and is endemic to certain parts of Asia, Africa, the Middle East and South America. Despite having a much smaller genome than that of B. pseudomallei, both share genes with an average identity of 99% at the nucleotide level (reviewed by Galyov et al., 2010).Burkholderia species form a monophyletic group within the Burkholderiales order of the Betaproteobacteria. Within the genus, there are three distinct monophyletic clusters, one of which is the clade comprising B. pseudomallei and closely related species.

Burkholderia pseudomallei causes the human disease melioidosis, which is notoriously difficult to diagnose due to widely differing clinical manifestations. It may present as flu-like symptoms, benign pneumonitis, acute and chronic pneumonia, or fulminating septicemia. Infection occurs via inhalation of contaminated aerosol particles (e.g. during heavy rainfall) or through skin abrasions. Melioidosis commonly affects the lungs and is characterized by the spread of bacteria to different internal organs (e.g. spleen and liver), bacteraemia and a high mortality rate (19-51%). B. pseudomallei is refractory to most antibiotics and the response to treatments such as ceftazidime, carbapenems, TMP-SMZ, chloramphenicol and/or Augmentin is often slow or ineffective (reviewed by Galyov et al., 2010).

Burkholderia mallei causes the zoonosis glanders, which primarily affects horses although mules, donkeys, goats, dogs and cats may also act as hosts. In humans, infection occurs by contact with infected animals via the cutaneous or respiratory route. The clinical manifestations of the disease include febrile pneumonia associated with necrosis of the tracheobronchial tree or pustular skin lesions and the development of abscesses. Most patients become bacteremic and necrosis of the liver and spleen rapidly progresses. Even with antibiotic treatment, the mortality rate for human glanders is 50% (reviewed by Saikh & Mott, 2017)..

Both B. mallei and B. pseudomallei are able to invade and multiply within a variety of eukaryotic cells, where they are shielded from the host humoral immune response and antibiotics. Once internalized, they escape from endocytic vacuoles and enter the cytoplasm where they multiply and spread by being pushed to neighbouring cells using their actin tails and membrane protrusions (reviewed by Galyov et al., 2010).

The disease has been eradicated from the US and UK, but it is still endemic in Asia, Africa, Central and South America, and the Middle East. With more of the world’s population becoming diabetic or otherwise immunocompromised there is increasing interest in these diseases because both B. mallei and its close relative B. pseudomallei can cause opportunistic infections in these patient populations (reviewed by Saikh & Mott, 2017). Presently, there is no approved vaccine against B. mallei and B. pseudomallei infections but progress in vaccine development has shown that live attenuated vaccine strains are the most effective in protection and providing long-lasting immune responses against both diseases. Both diseases are challenging for clinical identification and laboratory diagnostics and delays in proper treatment result in high mortality rates. Therefore, an effective vaccine against glanders and melioidosis is urgently needed for disease prevention (Khakhum et al., 2019).

References

• Galyov et al. (2010). Molecular Insights into Burkholderia pseudomallei and Burkholderia mallei Pathogenesis. Annual Review of Microbiology. Vol. 64:495-517.
• Khakhum et al. (2019). Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis. PLoS Negl Trop Dis 13(7): e0007578.
• Saikh KU & Mott TM (2017). Innate immune response to Burkholderia mallei. Curr Opin Infect Dis. 30(3):297-302.