Genomics

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Genome-Wide Mapping of Growth Regulated Genes in Burkholderia pseudomallei


ABSTRACT: Many microbial pathogens express specific virulence traits at distinct growth phases. To investigate the molecular pathways linking bacterial growth to pathogenicity, we characterized the genome-wide growth transcriptome of the tropical pathogen Burkholderia pseudomallei (Bp), the causative agent of melioidosis. Using fine-scale sampling, approximately 17% of all Bp genes were found to display regulated expression during growth, manifested primarily as discrete waves of gene expression tightly associated with distinct growth phases and transition points. A functional curation of these clusters provided evidence of a global ‘just-in-time’ production strategy to ensure the synthesis of molecular constituents only when needed. We observed regulation of multiple virulence factors at all growth phases, and by analyzing the early-phase transcriptome data, we identified and experimentally validated serC as a novel virulence factor in mice. Immunization of mice with serC-disrupted Bp also conferred protection against subsequent challenges with different wild-type Bp strains, demonstrating the potential utility of the serC mutant as an attenuated vaccine. We found a significant bias in early phase genes on Chromosome 1, supporting its proposed role as the ancestral Burkholderia chromosome, and utilized a chromosomally ordered co-expression metric to define ~100 putative operons throughout the Bp genome. These results extend our knowledge of virulence pathways in Bp, and suggest that molecular events at all growth phases, including early phase, are likely to play important roles in microbial pathogenicity." Keywords: Time Series Comparison Bp (K96243)

ORGANISM(S): Burkholderia pseudomallei K96243

PROVIDER: GSE5495 | GEO | 2006/10/01

SECONDARY ACCESSION(S): PRJNA96135

REPOSITORIES: GEO

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