title: Integrative genomic, transcriptional, and proteomic diversity in natural isolates of the human pathogen Burkholderia pseudomallei.
abstract: 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.
authors.affiliation: Agenica Research, Singapore, Republic of Singapore.
authors.forename: Keli
authors.initials: K
authors.lastname: Ou
authors.forename: Catherine
authors.initials: C
authors.lastname: Ong
authors.forename: Shze Yung
authors.initials: SY
authors.lastname: Koh
authors.forename: Fiona
authors.initials: F
authors.lastname: Rodrigues
authors.forename: Siew Hoon
authors.initials: SH
authors.lastname: Sim
authors.forename: Daniel
authors.initials: D
authors.lastname: Wong
authors.forename: Chia Huey
authors.initials: CH
authors.lastname: Ooi
authors.forename: Kim Chong
authors.initials: KC
authors.lastname: Ng
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Jikuya
authors.forename: Chin Chin
authors.initials: CC
authors.lastname: Yau
authors.forename: Sou Yen
authors.initials: SY
authors.lastname: Soon
authors.forename: Djohan
authors.initials: D
authors.lastname: Kesuma
authors.forename: May Ann
authors.initials: MA
authors.lastname: Lee
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D016957:Burkholderia pseudomallei / Q000235:genetics*; D020869:Gene Expression Profiling; D014644:Genetic Variation; D016680:Genome, Bacterial; D010641:Phenotype; D020033:Protein Isoforms / Q000235:genetics; D020543:Proteome; D013045:Species Specificity; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D020033:Protein Isoforms; D020543:Proteome