This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ou, K. Articles by Tan, P. Search for Related Content PubMed PubMed Citation Articles by Ou, K. Articles by Tan, P.

Integrative Genomic, Transcriptional, and Proteomic Diversity in Natural Isolates of the Human Pathogen Burkholderia pseudomallei

Keli Ou,^1,4, Catherine Ong,^2, Shze Yung Koh,^3, Fiona Rodrigues,³ Siew Hoon Sim,² Daniel Wong,³ Chia Huey Ooi,³ Kim Chong Ng,³ Hiroyuki Jikuya,^1,4 Chin Chin Yau,^1,4 Sou Yen Soon,^1,4 Djohan Kesuma,¹ May Ann Lee,² and Patrick Tan^1,3,5*

Agenica Research,¹ National Cancer Centre,³ Genome Institute of Singapore, 11 Hospital Drive, Singapore 169610, Republic of Singapore,⁵ Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, Singapore 117510, Republic of Singapore,² Shimadzu (Asia Pacific), 16A Science Park Drive, Singapore Science Park 1, Singapore 118228, Republic of Singapore⁴

Received 11 December 2004/ Accepted 1 March 2005

Natural isolates of pathogenic bacteria can exhibit a broad range of phenotypic traits. To investigate the molecular mechanisms contributing to such phenotypic variability, we compared the genomes, transcriptomes, and proteomes of two natural isolates of the gram-negative bacterium Burkholderia pseudomallei, the causative agent of the human disease melioidosis. Significant intrinsic genomic, transcriptional, and proteomic variations were observed between the two strains involving genes of diverse functions. We identified 16 strain-specific regions in the B. pseudomallei K96243 reference genome, and for eight regions their differential presence could be ascribed to either DNA acquisition or loss. A remarkable 43% of the transcriptional differences between the strains could be attributed to genes that were differentially present between K96243 and Bp15682, demonstrating the importance of lateral gene transfer or gene loss events in contributing to pathogen diversity at the gene expression level. Proteins expressed in a strain-specific manner were similarly correlated at the gene expression level, but up to 38% of the global proteomic variation between strains comprised proteins expressed in both strains but associated with strain-specific protein isoforms. Collectively, >65 hypothetical genes were transcriptionally or proteomically expressed, supporting their bona fide biological presence. Our results provide, for the first time, an integrated framework for classifying the repertoire of natural variations existing at distinct molecular levels for an important human pathogen.

These authors contributed equally to this report.

This article has been cited by other articles:

• Bertin, P. N., Medigue, C., Normand, P. (2008). Advances in environmental genomics: towards an integrated view of micro-organisms and ecosystems. Microbiology 154: 347-359 [Abstract] [Full Text]  
• Brilli, M., Fani, R., Lio, P. (2008). Current trends in the bioinformatic sequence analysis of metabolic pathways in prokaryotes. Brief Bioinform 9: 34-45 [Abstract] [Full Text]  
• Tuanyok, A., Auerbach, R. K., Brettin, T. S., Bruce, D. C., Munk, A. C., Detter, J. C., Pearson, T., Hornstra, H., Sermswan, R. W., Wuthiekanun, V., Peacock, S. J., Currie, B. J., Keim, P., Wagner, D. M. (2007). A Horizontal Gene Transfer Event Defines Two Distinct Groups within Burkholderia pseudomallei That Have Dissimilar Geographic Distributions. J. Bacteriol. 189: 9044-9049 [Abstract] [Full Text]  
• Rodrigues, F., Sarkar-Tyson, M., Harding, S. V., Sim, S. H., Chua, H. H., Lin, C. H., Han, X., Karuturi, R. K. M., Sung, K., Yu, K., Chen, W., Atkins, T. P., Titball, R. W., Tan, P. (2006). Global Map of Growth-Regulated Gene Expression in Burkholderia pseudomallei, the Causative Agent of Melioidosis. J. Bacteriol. 188: 8178-8188 [Abstract] [Full Text]  
• Breitbach, K., Klocke, S., Tschernig, T., van Rooijen, N., Baumann, U., Steinmetz, I. (2006). Role of Inducible Nitric Oxide Synthase and NADPH Oxidase in Early Control of Burkholderia pseudomallei Infection in Mice. Infect. Immun. 74: 6300-6309 [Abstract] [Full Text]  
• Boddey, J. A., Flegg, C. P., Day, C. J., Beacham, I. R., Peak, I. R. (2006). Temperature-Regulated Microcolony Formation by Burkholderia pseudomallei Requires pilA and Enhances Association with Cultured Human Cells. Infect. Immun. 74: 5374-5381 [Abstract] [Full Text]  
• Duangsonk, K., Gal, D., Mayo, M., Hart, C. A., Currie, B. J., Winstanley, C. (2006). Use of a Variable Amplicon Typing Scheme Reveals Considerable Variation in the Accessory Genomes of Isolates of Burkholderia pseudomallei. J. Clin. Microbiol. 44: 1323-1334 [Abstract] [Full Text]