title: Global map of growth-regulated gene expression in Burkholderia pseudomallei, the causative agent of melioidosis.
abstract: Many microbial pathogens express specific virulence traits at distinct growth phases. To understand the molecular pathways linking bacterial growth to pathogenicity, we have characterized the growth transcriptome of Burkholderia pseudomallei, the causative agent of melioidosis. Using a fine-scale sampling approach, we found approximately 17% of all B. pseudomallei genes displaying regulated expression during growth in rich medium, occurring as broad waves of functionally coherent gene expression tightly associated with distinct growth phases and transition points. We observed regulation of virulence genes across all growth phases and identified serC as a potentially new virulence factor by virtue of its coexpression with other early-phase virulence genes. serC-disrupted B. pseudomallei strains were serine auxotrophs and in mouse infection assays exhibited a dramatic attenuation of virulence compared to wild-type B. pseudomallei. Immunization of mice with serC-disrupted B. pseudomallei also conferred protection against subsequent challenges with different wild-type B. pseudomallei strains. At a genomic level, early-phase genes were preferentially localized on chromosome 1, while stationary-phase genes were significantly biased towards chromosome 2. We detected a significant level of chromosomally clustered gene expression, allowing us to predict approximately 100 potential operons in the B. pseudomallei genome. We computationally and experimentally validated these operons by showing that genes in these regions are preferentially transcribed in the same 5'-->3' direction, possess significantly shorter intergenic lengths than the overall genome, and are expressed as a common mRNA transcript. The availability of this transcriptome map provides an important resource for understanding the transcriptional architecture of B. pseudomallei.
authors.affiliation: Genome Institute of Singapore, 60 Biopolis Street, no. 02-01, Genome, Singapore 138672, Republic of Singapore.
authors.forename: Fiona
authors.initials: F
authors.lastname: Rodrigues
authors.forename: Mitali
authors.initials: M
authors.lastname: Sarkar-Tyson
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Harding
authors.forename: Siew Hoon
authors.initials: SH
authors.lastname: Sim
authors.forename: Hui Hoon
authors.initials: HH
authors.lastname: Chua
authors.forename: Chi Ho
authors.initials: CH
authors.lastname: Lin
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.forename: R Krishna M
authors.initials: RK
authors.lastname: Karuturi
authors.forename: Ken
authors.initials: K
authors.lastname: Sung
authors.forename: Kun
authors.initials: K
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Atkins
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage; D016957:Burkholderia pseudomallei / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity; D002876:Chromosomes, Bacterial / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D016680:Genome, Bacterial; D008554:Melioidosis / Q000382:microbiology* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D014611:Vaccination; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001428:Bacterial Vaccines; D037521:Virulence Factors