Identification of the Lipopolysaccharide Modifications Controlled by the Salmonella PmrA/PmrB System Mediating Resistance to Fe(III) and Al(III)

Mol Microbiol. 2006 Aug;61(3):645-54. doi: 10.1111/j.1365-2958.2006.05273.x. Epub 2006 Jun 27.

Abstract

Iron is an essential metal but can be toxic in excess. While several homeostatic mechanisms prevent oxygen-dependent killing promoted by Fe(II), little is known about how cells cope with Fe(III), which kills by oxygen-independent means. Several Gram-negative bacterial species harbour a regulatory system - termed PmrA/PmrB - that is activated by and required for resistance to Fe(III). We now report the identification of the PmrA-regulated determinants mediating resistance to Fe(III) and Al(III) in Salmonella enterica serovar Typhimurium. We establish that these determinants remodel two regions of the lipopolysaccharide, decreasing the negative charge of this major constituent of the outer membrane. Remodelling entails the covalent modification of the two phosphates in the lipid A region with phosphoethanolamine and 4-aminoarabinose, which has been previously implicated in resistance to polymyxin B, as well as dephosphorylation of the Hep(II) phosphate in the core region by the PmrG protein. A mutant lacking the PmrA-regulated Fe(III) resistance genes bound more Fe(III) than the wild-type strain and was defective for survival in soil, suggesting that these PmrA-regulated lipopolysaccharide modifications aid Salmonella's survival and spread in non-host environments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Drug Resistance, Bacterial / genetics*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial
  • Iron / metabolism
  • Iron / pharmacology*
  • Lipid A / metabolism
  • Lipopolysaccharides
  • Molecular Sequence Data
  • Mutation
  • Periplasm / metabolism
  • Phosphoric Monoester Hydrolases / drug effects
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / metabolism
  • Phosphorylation
  • Polymyxin B / pharmacology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*
  • Soil Microbiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Bacterial Proteins
  • Escherichia coli Proteins
  • Lipid A
  • Lipopolysaccharides
  • PbgP protein, Yersinia pestis
  • PmrB protein, bacteria
  • PmrC protein, E coli
  • Transcription Factors
  • Ugd protein, Yersinia pestis
  • pmrA protein, Bacteria
  • Aluminum
  • Iron
  • Phosphoric Monoester Hydrolases
  • Polymyxin B