The pmrF Polymyxin-Resistance Operon of Yersinia Pseudotuberculosis Is Upregulated by the PhoP-PhoQ Two-Component System but Not by PmrA-PmrB, and Is Not Required for Virulence

Microbiology. 2004 Dec;150(Pt 12):3947-57. doi: 10.1099/mic.0.27426-0.


The Yersinia pseudotuberculosis chromosome contains a seven-gene polycistronic unit (the pmrF operon) whose products share extensive homologies with their pmrF counterparts in Salmonella enterica serovar Typhimurium (S. typhimurium), another Gram-negative bacterial enteropathogen. This gene cluster is essential for addition of 4-aminoarabinose to the lipid moiety of LPS, as demonstrated by MALDI-TOF mass spectrometry of lipid A from both wild-type and pmrF-mutated strains. As in S. typhimurium, 4-aminoarabinose substitution of lipid A contributes to in vitro resistance of Y. pseudotuberculosis to the antimicrobial peptide polymyxin B. Whereas pmrF expression in S. typhimurium is mediated by both the PhoP-PhoQ and PmrA-PmrB two-component regulatory systems, it appears to be PmrA-PmrB-independent in Y. pseudotuberculosis, with the response regulator PhoP interacting directly with the pmrF operon promoter region. This result reveals that the ubiquitous PmrA-PmrB regulatory system controls different regulons in distinct bacterial species. In addition, pmrF inactivation in Y. pseudotuberculosis has no effect on bacterial virulence in the mouse, again in contrast to the situation in S. typhimurium. The marked differences in pmrF operon regulation in these two phylogenetically close bacterial species may be related to their dissimilar lifestyles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Drug Resistance, Bacterial / genetics
  • Female
  • Gene Expression Regulation, Bacterial*
  • Mice
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Operon*
  • Polymyxins / pharmacology*
  • Sequence Analysis, DNA
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation
  • Virulence
  • Yersinia pseudotuberculosis / drug effects
  • Yersinia pseudotuberculosis / genetics
  • Yersinia pseudotuberculosis / pathogenicity*
  • Yersinia pseudotuberculosis Infections / microbiology
  • Yersinia pseudotuberculosis Infections / physiopathology


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • PhoQ protein, Bacteria
  • PmrB protein, bacteria
  • Polymyxins
  • Transcription Factors
  • pmrA protein, Bacteria
  • PhoP protein, Bacteria

Associated data

  • GENBANK/AF333125
  • GENBANK/AF336802
  • GENBANK/AY259243