Characterization and analysis of the Burkholderia pseudomallei BsaN virulence regulon

Yahua Chen, Imke Schröder, Christopher T. French, Artur Jaroszewicz, Xiao Jie Yee, Boon Eng Teh, Isabelle J. Toesca, Jeff F. Miller, Yunn Hwen Gan

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Background: Burkholderia pseudomallei is a facultative intracellular pathogen and the causative agent of melioidosis. A conserved type III secretion system (T3SS3) and type VI secretion system (T6SS1) are critical for intracellular survival and growth. The T3SS3 and T6SS1 genes are coordinately and hierarchically regulated by a TetR-type regulator, BspR. A central transcriptional regulator of the BspR regulatory cascade, BsaN, activates a subset of T3SS3 and T6SS1 loci. Results: To elucidate the scope of the BsaN regulon, we used RNAseq analysis to compare the transcriptomes of wild-type B. pseudomallei KHW and a bsaN deletion mutant. The 60 genes positively-regulated by BsaN include those that we had previously identified in addition to a polyketide biosynthesis locus and genes involved in amino acid biosynthesis. BsaN was also found to repress the transcription of 51 genes including flagellar motility loci and those encoding components of the T3SS3 apparatus. Using a promoter-lacZ fusion assay in E. coli, we show that BsaN together with the chaperone BicA directly control the expression of the T3SS3 translocon, effector and associated regulatory genes that are organized into at least five operons (BPSS1516-BPSS1552). Using a mutagenesis approach, a consensus regulatory motif in the promoter regions of BsaN-regulated genes was shown to be essential for transcriptional activation. Conclusions: BsaN/BicA functions as a central regulator of key virulence clusters in B. pseudomallei within a more extensive network of genetic regulation. We propose that BsaN/BicA controls a gene expression program that facilitates the adaption and intracellular survival of the pathogen within eukaryotic hosts.

Original languageEnglish (US)
Article number206
JournalBMC microbiology
Volume14
Issue number1
DOIs
StatePublished - Aug 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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