Abstract
BackgroundBurkholderia pseudomallei is a human pathogen causing severe infections in tropical and subtropical regions and is classified as a bio-threat agent. B. thailandensis strain E264 has been proposed as less pathogenic surrogate for understanding the interactions of B. pseudomallei with host cells.ResultsWe show that, unlike B. thailandensis strain E264, the pattern of growth of B. thailandensis strain E555 in macrophages is similar to that of B. pseudomallei. We have genome sequenced B. thailandensis strain E555 and using the annotated sequence identified genes and proteins up-regulated during infection. Changes in gene expression identified more of the known B. pseudomallei virulence factors than changes in protein levels and used together we identified 16% of the currently known B. pseudomallei virulence factors. These findings demonstrate the utility of B. thailandensis strain E555 to study virulence of B. pseudomallei.ConclusionsA weakness of studies using B. thailandensis as a surrogate for B. pseudomallei is that the strains used replicate at a slower rate in infected cells. We show that the pattern of growth of B. thailandensis strain E555 in macrophages closely mirrors that of B. pseudomallei. Using this infection model we have shown that virulence factors of B. pseudomallei can be identified as genes or proteins whose expression is elevated on the infection of macrophages. This finding confirms the utility of B. thailandensis strain E555 as a surrogate for B. pseudomallei and this strain should be used for future studies on virulence mechanisms.
Highlights
Burkholderia pseudomallei is a human pathogen causing severe infections in tropical and subtropical regions and is classified as a bio-threat agent
Genome sequencing We selected B. thailandensis strain E555 for our study because, unlike most B. thailandensis strains, it possesses a capsular polysaccharide which is similar to B. pseudomallei [40, 41]
The remaining 914 proteins were not found in either B. thailandensis strain and of these 233 were encoded by genes located in the genome islands in B. pseudomallei
Summary
Burkholderia pseudomallei is a human pathogen causing severe infections in tropical and subtropical regions and is classified as a bio-threat agent. The bacterial pathogen Burkholderia pseudomallei causes meliodosis, a severe disease of humans in tropical and subtropical regions [1,2,3]. Community-acquired disease is most likely a consequence of the bacterium in soil or water entering through cuts or skin abrasions. In small animal models of disease, the bacterium is much more infective. Whilst a range of studies have characterized some of the virulence factors of B. pseudomallei [2, 12,13,14], it is clear that a much broader range of genes and proteins are implicated in playing a role in disease [13, 15, 16]. Studies on virulence of the bacterium are necessarily constrained by the requirement to handle the bacterium under containment level 3 conditions
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