title: Genomic patterns of pathogen evolution revealed by comparison of Burkholderia pseudomallei, the causative agent of melioidosis, to avirulent Burkholderia thailandensis.
abstract: BACKGROUND
  The Gram-negative bacterium Burkholderia pseudomallei (Bp) is the causative agent of the human disease melioidosis. To understand the evolutionary mechanisms contributing to Bp virulence, we performed a comparative genomic analysis of Bp K96243 and B. thailandensis (Bt) E264, a closely related but avirulent relative.
  
  
  RESULTS
  We found the Bp and Bt genomes to be broadly similar, comprising two highly syntenic chromosomes with comparable numbers of coding regions (CDs), protein family distributions, and horizontally acquired genomic islands, which we experimentally validated to be differentially present in multiple Bt isolates. By examining species-specific genomic regions, we derived molecular explanations for previously-known metabolic differences, discovered potentially new ones, and found that the acquisition of a capsular polysaccharide gene cluster in Bp, a key virulence component, is likely to have occurred non-randomly via replacement of an ancestral polysaccharide cluster. Virulence related genes, in particular members of the Type III secretion needle complex, were collectively more divergent between Bp and Bt compared to the rest of the genome, possibly contributing towards the ability of Bp to infect mammalian hosts. An analysis of pseudogenes between the two species revealed that protein inactivation events were significantly biased towards membrane-associated proteins in Bt and transcription factors in Bp.
  
  
  CONCLUSIONS
  Our results suggest that a limited number of horizontal-acquisition events, coupled with the fine-scale functional modulation of existing proteins, are likely to be the major drivers underlying Bp virulence. The extensive genomic similarity between Bp and Bt suggests that, in some cases, Bt could be used as a possible model system for studying certain aspects of Bp behavior.
authors.affiliation: Genome Institute of Singapore, Singapore 138672, Republic of Singapore. yuy@gis.a-star.edu.sg
authors.forename: Yiting
authors.initials: Y
authors.lastname: Yu
authors.forename: H Stanley
authors.initials: HS
authors.lastname: Kim
authors.forename: Hui Hoon
authors.initials: HH
authors.lastname: Chua
authors.forename: Chi Ho
authors.initials: CH
authors.lastname: Lin
authors.forename: Siew Hoon
authors.initials: SH
authors.lastname: Sim
authors.forename: Daoxun
authors.initials: D
authors.lastname: Lin
authors.forename: Alan
authors.initials: A
authors.lastname: Derr
authors.forename: Reinhard
authors.initials: R
authors.lastname: Engels
authors.forename: David
authors.initials: D
authors.lastname: DeShazer
authors.forename: Bruce
authors.initials: B
authors.lastname: Birren
authors.forename: William C
authors.initials: WC
authors.lastname: Nierman
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D019117:Burkholderia / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016957:Burkholderia pseudomallei / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016680:Genome, Bacterial; D010802:Phylogeny; D014774:Virulence