Transcriptional regulation of the 4-amino-4-deoxy-L-arabinose biosynthetic genes in Yersinia pestis

J Biol Chem. 2005 Apr 15;280(15):14765-72. doi: 10.1074/jbc.M413900200. Epub 2005 Feb 14.

Abstract

Inducible membrane remodeling is an adaptive mechanism that enables Gram-negative bacteria to resist killing by cationic antimicrobial peptides and to avoid eliciting an immune response. Addition of 4-amino-4-deoxy-l -arabinose (4-aminoarabinose) moieties to the phosphate residues of the lipid A portion of the lipopolysaccharide decreases the net negative charge of the bacterial membrane resulting in protection from the cationic antimicrobial peptide polymyxin B. In Salmonella enterica serovar Typhimurium, the PmrA/PmrB two-component regulatory system governs resistance to polymyxin B by controlling transcription of the 4-aminoarabinose biosynthetic genes. Transcription of PmrA-activated genes is induced by Fe(3+), which is sensed by PmrA cognate sensor PmrB, and by low Mg(2+), in a mechanism that requires not only the PmrA and PmrB proteins but also the Mg(2+)-responding PhoP/PhoQ system and the PhoP-activated PmrD protein, a post-translational activator of the PmrA protein. Surprisingly, Yersinia pestis can promote PhoP-dependent modification of its lipid A with 4-aminoarabinose despite lacking a PmrD protein. Here we report that Yersinia uses different promoters to transcribe the 4-aminoarabinose biosynthetic genes pbgP and ugd depending on the inducing signal. This is accomplished by the presence of distinct binding sites for the PmrA and PhoP proteins in the promoters of the pbgP and ugd genes. Our results demonstrate that closely related bacterial species may use disparate regulatory pathways to control genes encoding conserved proteins.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Sugars / biosynthesis*
  • Amino Sugars / genetics*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Proliferation
  • DNA Primers / chemistry
  • Deoxyribonuclease I / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Bacterial*
  • Iron / chemistry
  • Iron / metabolism
  • Lipid A / chemistry
  • Magnesium / chemistry
  • Magnesium / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Plasmids / metabolism
  • Polymyxin B / chemistry
  • Polymyxin B / pharmacology
  • Promoter Regions, Genetic
  • Salmonella enterica / metabolism
  • Single-Strand Specific DNA and RNA Endonucleases / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Yersinia pestis / enzymology*
  • Yersinia pestis / genetics*

Substances

  • Amino Sugars
  • Bacterial Proteins
  • DNA Primers
  • Lipid A
  • PbgP protein, Yersinia pestis
  • PmrB protein, bacteria
  • Transcription Factors
  • Ugd protein, Yersinia pestis
  • pmrA protein, Bacteria
  • PhoP protein, Bacteria
  • 4-amino-4-deoxyarabinose
  • Iron
  • Deoxyribonuclease I
  • Single-Strand Specific DNA and RNA Endonucleases
  • Magnesium
  • Polymyxin B