Abstract
BackgroundThe bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei.ResultsUsing bacteriophage-mediated immunoscreening we identified genes expressed in vivo during experimental equine glanders infection. A family of immunodominant antigens were identified that share protein domain architectures with hemagglutinins and invasins. These have been designated Burkholderia Hep_Hag autotransporter (BuHA) proteins. A total of 110/207 positive clones (53%) of a B. mallei expression library screened with sera from two infected horses belonged to this family. This contrasted with 6/189 positive clones (3%) of a B. pseudomallei expression library screened with serum from 21 patients with culture-proven melioidosis.ConclusionMembers of the BuHA proteins are found in other Gram-negative bacteria and have been shown to have important roles related to virulence. Compared with other bacterial species, the genomes of both B. mallei and B. pseudomallei contain a relative abundance of this family of proteins. The domain structures of these proteins suggest that they function as multimeric surface proteins that modulate interactions of the cell with the host and environment. Their effect on the cellular immune response to B. mallei and their potential as diagnostics for glanders requires further study.
Highlights
The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively
There is a need to develop an effective vaccine for individuals at risk of exposure from deliberate release, and understanding the immune response elicited during infection with B. mallei is central to this process
B. mallei expression library screening with glanders serum The B. mallei expression library was individually probed with sera from two experimentally infected horses taken seven days after intra-tracheal bacterial inoculation with B. mallei ATCC 23344
Summary
The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei. Burkholderia mallei is the causative agent of glanders, a serious Gram-negative infection that predominantly affects horses and other equines [1]. There is a need to develop an effective vaccine for individuals at risk of exposure from deliberate release, and understanding the immune response elicited during infection with B. mallei is central to this process. The relative importance of cellular versus humoral responses in the development of protective immunity against B. mallei is under investigation. One study of murine monoclonal antibodies (mAbs) against B. mallei administered to mice prior to a lethal aerosol challenge reported non-sterilizing protection [6]. Passive protection in the mouse model has been described for the highly related B. pseudomallei using murine mAbs specific for B. pseudomallei polysaccharide [7]
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