Structural flexibility in the Burkholderia mallei genome

Abstract

The complete genome sequence of Burkholderia mallei ATCC 23344 provides insight into this highly infectious bacterium's pathogenicity and evolutionary history. B. mallei, the etiologic agent of glanders, has come under renewed scientific investigation as a result of recent concerns about its past and potential future use as a biological weapon. Genome analysis identified a number of putative virulence factors whose function was supported by comparative genome hybridization and expression profiling of the bacterium in hamster liver in vivo. The genome contains numerous insertion sequence elements that have mediated extensive deletions and rearrangements of the genome relative to Burkholderia pseudomallei. The genome also contains a vast number (>12,000) of simple sequence repeats. Variation in simple sequence repeats in key genes can provide a mechanism for generating antigenic variation that may account for the mammalian host's inability to mount a durable adaptive immune response to a B. mallei infection.

Fig. 2.

Putative virulence genes revealed by comparative genome hybridization analysis. A total 156 genes diverged or absent in at least one of the three avirulent isolates were compared across the virulent isolates by using hierarchical clustering. Eighty genes that show little or no variation in virulent isolates were found in three different locations in the cluster, denoted as groups 1–3. Putative virulence genes and the genes shown to be highly expressed in hamster spleen (see Table 9) are highlighted. B. mallei isolates used for this study, microarray hybridization pairs, and a graph of gene distribution by chromosomes are also shown.

Fig. 1.

Circular diagrams of chromosome 1 and chromosome 2 in B. mallei. Locations of selected genome features are denoted on seven layers of circles. From the outermost layer, 1) CDS in color codes for predicted functional role categories, 2) CDS in the other orientation, 3) GC skew, 4) IS elements flanking syntenic breaks compared to B. pseudomallei chromosome, 5) IS elements not associated with syntenic breaks, 6) SSRs that contain at least one A or T in the repeat unit, and 7) putative virulence genes. The locations of wcb capsule gene cluster, lipopolysaccharide biosynthesis genes, and a singleton luxR-type regulator in chromosome 1, plant and animal pathogen-type type III secretion system loci, and two pairs of luxR/luxI-type regulators in chromosome 2 are shown.