Abstract
BackgroundBurkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease – from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. About ninety five percent of patients succumb to untreated septicemic infections and the fatality rate is 50 % even when standard antibiotic treatments are administered.ResultsThe goal of this study is to profile murine macrophage-mediated phenotypic and molecular responses that are characteristic to a collection of Bp, Bm, Burkholderia thailandensis (Bt) and Burkholderia oklahomensis (Bo) strains obtained from humans, animals, environment and geographically diverse locations. Burkholderia spp. (N = 21) were able to invade and replicate in macrophages, albeit to varying degrees. All Bp (N = 9) and four Bm strains were able to induce actin polymerization on the bacterial surface following infection. Several Bp and Bm strains showed reduced ability to induce multinucleated giant cell (MNGC) formation, while Bo and Bp 776 were unable to induce this phenotype. Measurement of host cytokine responses revealed a statistically significant Bm mediated IL-6 and IL-10 production compared to Bp strains. Hierarchical clustering of transcriptional data from 84 mouse cytokines, chemokines and their corresponding receptors identified 29 host genes as indicators of differential responses between the Burkholderia spp. Further validation confirmed Bm mediated Il-1b, Il-10, Tnfrsf1b and Il-36a mRNA expressions were significantly higher when compared to Bp and Bt.ConclusionsThese results characterize the phenotypic and immunological differences in the host innate response to pathogenic and avirulent Burkholderia strains and provide insight into the phenotypic alterations and molecular targets underlying host-Burkholderia interactions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0593-3) contains supplementary material, which is available to authorized users.
Highlights
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively
Diverse Burkholderia spp. are phagocytized and replicate within RAW264.7 macrophages A diverse collection of Bp (N = 9), Bm (N = 5), Burkholderia thailandensis (Bt) (N = 3) and Burkholderia oklahomensis (Bo) (N = 1) strains from various geographical locations throughout the world were examined in this study
The three Bt strains CDC3015869, Phuket 4 W-1, DW503 and Bo E0147 were internalized and able to replicate in RAW264.7 macrophages (Fig. 1a)
Summary
Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm) are Gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. Depending on the route of exposure, aerosol or transcutaneous, infection by Bp or Bm can result in an extensive range of disease – from acute to chronic, relapsing illness to fatal septicemia. Both diseases are associated with difficult diagnosis and high fatality rates. Clinical signs of melioidosis may manifest as flu-like symptoms, pneumonia, or fulminating septicemia that are often fatal [1, 4] Both chronic and acute forms of melioidosis have been reported and the pathogen can colonize a diverse range of tissues including liver, spleen, lung, skin and even the urinary tract. Due to the highly infectious nature of Bp and Bm, in particular for exposure by the aerosol route, both pathogens are considered potential biological warfare threat agents and are classified by the federal select agent program as Tier 1 select agents
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