Genomic patterns of pathogen evolution revealed by comparison of Burkholderia pseudomallei, the causative agent of melioidosis, to avirulent Burkholderia thailandensis

Yiting Yu¹ , H Stanley Kim³ , Hui Hoon Chua¹ , Chi Ho Lin¹ , Siew Hoon Sim⁴ , Daoxun Lin¹ , Alan Derr⁵ , Reinhard Engels⁵ , David DeShazer⁶ , Bruce Birren⁵ , William C Nierman³ and Patrick Tan¹^,2

¹Genome Institute of Singapore, Singapore 138672, Republic of Singapore

²National Cancer Centre, Singapore 169610, Republic of Singapore

³The Institute for Genomic Research, Rockville, MD 20850, USA

⁴Defense Medical and Environmental Research Institute (DMERI), DSO National Laboratories, Singapore 117510, Republic of Singapore

⁵The Broad Institute, Cambridge, MA 02141, USA

⁶Bacteriology Division, US Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA

author email corresponding author email

BMC Microbiology 2006, 6:46doi:10.1186/1471-2180-6-46


Published:	26 May 2006

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.

Conclusion

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.