Regulation of Burkholderia cenocepacia virulence by the fatty acyl-CoA ligase DsfR as a response regulator of quorum sensing signal

Cell Rep. 2024 May 28;43(5):114223. doi: 10.1016/j.celrep.2024.114223. Epub 2024 May 14.

Abstract

Quorum sensing (QS) is a cell-to-cell communication mechanism mediated by small diffusible signaling molecules. Previous studies showed that RpfR controls Burkholderia cenocepacia virulence as a cis-2-dodecenoic acid (BDSF) QS signal receptor. Here, we report that the fatty acyl-CoA ligase DsfR (BCAM2136), which efficiently catalyzes in vitro synthesis of lauryl-CoA and oleoyl-CoA from lauric acid and oleic acid, respectively, acts as a global transcriptional regulator to control B. cenocepacia virulence by sensing BDSF. We show that BDSF binds to DsfR with high affinity and enhances the binding of DsfR to the promoter DNA regions of target genes. Furthermore, we demonstrate that the homolog of DsfR in B. lata, RS02960, binds to the target gene promoter, and perception of BDSF enhances the binding activity of RS02960. Together, these results provide insights into the evolved unusual functions of DsfR that control bacterial virulence as a response regulator of QS signal.

Keywords: CP: Microbiology; CP: Molecular biology.

MeSH terms

  • Animals
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Burkholderia cenocepacia* / genetics
  • Burkholderia cenocepacia* / metabolism
  • Burkholderia cenocepacia* / pathogenicity
  • Coenzyme A Ligases* / genetics
  • Coenzyme A Ligases* / metabolism
  • Fatty Acids, Monounsaturated / metabolism
  • Gene Expression Regulation, Bacterial*
  • Lauric Acids / metabolism
  • Mice
  • Promoter Regions, Genetic*
  • Protein Binding
  • Quorum Sensing* / genetics
  • Signal Transduction
  • Virulence

Substances

  • Bacterial Proteins
  • Coenzyme A Ligases
  • 2-dodecenoic acid
  • Fatty Acids, Monounsaturated
  • Lauric Acids