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

Yixin Shi, Michael J. Cromie, Fong Fu Hsu, John Turk, Eduardo A. Groisman

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

In Salmonella enterica, the PhoP-PhoQ two-component system governs resistance to structurally different antimicrobial peptides including the alpha-helical magainin 2, the β-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.

Original languageEnglish (US)
Pages (from-to)229-241
Number of pages13
JournalMolecular Microbiology
Volume53
Issue number1
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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