Project description:Bacterial transcriptomes are dynamic, context-specific and condition-dependent. Infection by the soil bacterium, Burkholderia pseudomallei, causes melioidosis, an often fatal infectious disease of humans and animals. Possessing a large multi-chromosomal genome, B. pseudomallei is able to persist and survive in a multitude of environments. To obtain a comprehensive overview of B. pseudomallei expressed transcripts, we initiated whole-genome transcriptome profiling covering a broad spectrum of conditions and exposures – a so-called “condition compendium”. Using the compendium, we confirmed many previously-annotated genes and operons, and also identified hundreds of novel transcripts including anti-sense transcripts and non-coding RNAs. By systematically examining genes exhibiting highly similar expression patterns, we ascribed putative functions to previously uncharacterized genes, and identified novel regulatory elements controlling these expression patterns. We also used the compendium to elucidate candidate virulence pathways associated with quorum-sensing and infection in mice. Our study showcases the power of a B. pseudomallei condition compendium as a valuable resource for understanding microbial physiology and the pathogenesis of melioidosis.
Project description:Melioidosis is a neglected tropical disease caused by the Gram-negative bacterium Burkholderia pseudomallei. It is widespread in Southeast Asia and under-reported across tropical regions worldwide. Patients present with a range of clinical syndromes including sepsis, pneumonia and focal abscesses, with a mortality rate of 40% in hospitalized patients in Thailand. Up to two-thirds of patients with melioidosis have diabetes mellitus. In this experiment we sought to characterize pathways activated by whole killed B. pseudomallei bacteria and by three vaccine candidate proteins from B. pseudomallei, BPSL2520 (uncharacterized protein), BPSS1525 (BopE) and BPSL2096 (AhpC) in patients with diabetes and acute melioidosis.
