Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates
1 Genome Institute of Singapore, 60 Biopolis Street, 138672 Singapore
2 Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand
3 Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand
4 Scripps Translational Science Institute, The Scripps Research Institute, 3344 North Torrey Pines Court, Suite 300, La Jolla, CA 92037, USA
5 Department of Computer Science, National University of Singapore, 13 Computing Drive, 117417 Singapore
6 National Cancer Centre Singapore, 11 Hospital Drive, 169610 Singapore
7 Defense Medical and Environmental Research Institute, DSO National Laboratories, 27 Medical Drive, 117510 Singapore
8 Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, UK
9 Centers for Disease Control and Prevention, 1600 Clifton Road MS G-34, Atlanta, GA 30333, USA
10 Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
11 Duke-NUS Graduate Medical School, 8 College Road, 169857 Singapore
Genome Biology 2010, 11:R89 doi:10.1186/gb-2010-11-8-r89Published: 27 August 2010
Burkholderia thailandensis is a non-pathogenic environmental saprophyte closely related to Burkholderia pseudomallei, the causative agent of the often fatal animal and human disease melioidosis. To study B. thailandensis genomic variation, we profiled 50 isolates using a pan-genome microarray comprising genomic elements from 28 Burkholderia strains and species.
Of 39 genomic regions variably present across the B. thailandensis strains, 13 regions corresponded to known genomic islands, while 26 regions were novel. Variant B. thailandensis isolates exhibited isolated acquisition of a capsular polysaccharide biosynthesis gene cluster (B. pseudomallei-like capsular polysaccharide) closely resembling a similar cluster in B. pseudomallei that is essential for virulence in mammals; presence of this cluster was confirmed by whole genome sequencing of a representative variant strain (B. thailandensis E555). Both whole-genome microarray and multi-locus sequence typing analysis revealed that the variant strains formed part of a phylogenetic subgroup distinct from the ancestral B. thailandensis population and were associated with atypical isolation sources when compared to the majority of previously described B. thailandensis strains. In functional assays, B. thailandensis E555 exhibited several B. pseudomallei-like phenotypes, including colony wrinkling, resistance to human complement binding, and intracellular macrophage survival. However, in murine infection assays, B. thailandensis E555 did not exhibit enhanced virulence relative to other B. thailandensis strains, suggesting that additional factors are required to successfully colonize and infect mammals.
The discovery of such novel variant strains demonstrates how unbiased genomic surveys of non-pathogenic isolates can reveal insights into the development and emergence of new pathogenic species.