Identification of potential therapeutic targets for Burkholderia cenocepacia by comparative transcriptomics.

BACKGROUND

Burkholderia cenocepacia is an endemic soil dweller and emerging opportunistic pathogen in patients with cystic fibrosis (CF). The identification of virulence factors and potential therapeutic targets has been hampered by the genomic diversity within the species as many factors are not shared among the pathogenic members of the species.

METHODOLOGY/PRINCIPAL FINDINGS: In this study, global identification of putative virulence factors was performed by analyzing the transcriptome of two related strains of B. cenocepacia (one clinical, one environmental) under conditions mimicking cystic fibrosis sputum versus soil. Soil is a natural reservoir for this species; hence, genes induced under CF conditions relative to soil may represent adaptations that have occurred in clinical strains. Under CF conditions, several genes encoding proteins thought to be involved in virulence were induced and many new ones were identified. Our analysis, in combination with previous studies, reveals 458 strain-specific genes, 126 clinical-isolate-specific, and at least four species-specific genes that are induced under CF conditions. The chromosomal distribution of the induced genes was disproportionate to the size of the chromosome as genes expressed under soil conditions by both strains were more frequent on the second chromosome and those differentially regulated between strains were more frequent on the third chromosome. Conservation of these induced genes was established using the 11 available Bcc genome sequences to indicate whether potential therapeutic targets would be species-wide.

CONCLUSIONS/SIGNIFICANCE: Comparative transcriptomics is a useful way to identify new potential virulence factors and therapeutic targets for pathogenic bacteria. We identified eight genes induced under CF conditions that were also conserved in the Bcc and may constitute particularly attractive therapeutic targets due to their signal sequence, predicted cellular location, and homology to known therapeutic targets.