Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei

Abstract

Burkholderia pseudomallei is a recognized biothreat agent and the causative agent of melioidosis. This Gram-negative bacterium exists as a soil saprophyte in melioidosis-endemic areas of the world and accounts for 20% of community-acquired septicaemias in northeastern Thailand where half of those affected die. Here we report the complete genome of B. pseudomallei, which is composed of two chromosomes of 4.07 megabase pairs and 3.17 megabase pairs, showing significant functional partitioning of genes between them. The large chromosome encodes many of the core functions associated with central metabolism and cell growth, whereas the small chromosome carries more accessory functions associated with adaptation and survival in different niches. Genomic comparisons with closely and more distantly related bacteria revealed a greater level of gene order conservation and a greater number of orthologous genes on the large chromosome, suggesting that the two replicons have distinct evolutionary origins. A striking feature of the genome was the presence of 16 genomic islands (GIs) that together made up 6.1% of the genome. Further analysis revealed these islands to be variably present in a collection of invasive and soil isolates but entirely absent from the clonally related organism B. mallei. We propose that variable horizontal gene acquisition by B. pseudomallei is an important feature of recent genetic evolution and that this has resulted in a genetically diverse pathogenic species.

Fig. 1.

Schematic circular diagrams of the large and small chromosomes of the B. pseudomallei genome. Where appropriate, categories are shown as pairs of concentric circles representing both coding strands. Rings from outside to inside: GIs represented by red segments; scale (in Mb); annotated CDSs colored according to predicted function; additional CDSs compared to the sequenced B. mallei strain ATCC 2944; the percentage of G + C content plot; (G–C)/(G + C) deviation plot (>0%, olive; <0%, purple). Color coding for CDSs: dark blue, pathogenicity/adaptation; black, energy metabolism; red, information transfer; dark green, surface-associated; cyan, degradation of large molecules; magenta, degradation of small molecules; yellow, central/intermediary metabolism; pale green, unknown; pale blue, regulators; orange, conserved hypothetical; brown, pseudogenes; pink, phage plus IS elements; gray, miscellaneous.

Fig. 2.

Distribution of the CDSs belonging to different functional classes on the two chromosomes of B. pseudomallei. Figures for functional classes on each chromosome are expressed as a percentage of the total number of CDSs on that replicon.

Fig. 3.

Prevalence of GIs in environmental and invasive clinical isolates of B. psuedomallei. Distribution of GIs in environmental and invasive clinical B. pseudomallei isolates (n = 40) as determined by multiplex PCR.