PhoP-regulated Salmonella resistance to the antimicrobial peptides magainin 2 and polymyxin B

Mol Microbiol. 2004 Jul;53(1):229-41. doi: 10.1111/j.1365-2958.2004.04107.x.


In Salmonella enterica, the PhoP-PhoQ two-component system governs resistance to structurally different antimicrobial peptides including the alpha-helical magainin 2, the beta-sheet defensins and the cyclic lipopeptide polymyxin B. To identify the PhoP-regulated determinants mediating peptide resistance, we prepared a plasmid library from a phoP mutant, introduced it into a phoP mutant and selected for magainin-resistant clones. One of the clones harboured the PhoP-activated ugtL gene, deletion of which rendered Salmonella susceptible to magainin 2 and polymyxin B, but not defensin HNP-1. We established that ugtL encodes an inner membrane protein that promotes the formation of monophosphorylated lipid A in the lipopolysaccharide. Inactivation of both ugtL and the regulatory gene pmrA, which controls lipid A modifications required for resistance to polymxyin B (but not to magainin 2) and is post-transcriptionally activated by the PhoP-PhoQ system, resulted in a strain that was as susceptible to polymyxin B as a phoP mutant. The most frequently recovered clone harboured the yqjA gene, which we show is PhoP regulated and required for resistance to magainin 2 but not to polymyxin B or defensin HNP-1. Our results indicate that different PhoP-mediated modifications in lipid A are necessary for resistance to different antimicrobial peptides.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / physiology*
  • Drug Resistance, Bacterial / physiology*
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Microbial Sensitivity Tests
  • Peptides / pharmacology
  • Polymyxins / pharmacology*
  • Salmonella / drug effects*
  • Salmonella / genetics
  • Transcriptional Activation


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Peptides
  • Polymyxins
  • PhoP protein, Bacteria