Recognition of Antimicrobial Peptides by a Bacterial Sensor Kinase

Cell. 2005 Aug 12;122(3):461-72. doi: 10.1016/j.cell.2005.05.030.

Abstract

PhoQ is a membrane bound sensor kinase important for the pathogenesis of a number of Gram-negative bacterial species. PhoQ and its cognate response regulator PhoP constitute a signal-transduction cascade that controls inducible resistance to host antimicrobial peptides. We show that enzymatic activity of Salmonella typhimurium PhoQ is directly activated by antimicrobial peptides. A highly acidic surface of the PhoQ sensor domain participates in both divalent-cation and antimicrobial-peptide binding as a first step in signal transduction across the bacterial membrane. Identification of PhoQ signaling mutants, binding studies with the PhoQ sensor domain, and structural analysis of this domain can be incorporated into a model in which antimicrobial peptides displace divalent cations from PhoQ metal binding sites to initiate signal transduction. Our findings reveal a molecular mechanism by which bacteria sense small innate immune molecules to initiate a transcriptional program that promotes bacterial virulence.

Publication types

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

MeSH terms

  • Adaptation, Physiological / immunology
  • Antimicrobial Cationic Peptides / immunology
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacterial Proteins / drug effects
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Gene Expression Regulation, Bacterial
  • Host-Parasite Interactions / immunology
  • Humans
  • Magnesium / immunology
  • Models, Biological
  • Protein Binding
  • Protein Conformation
  • Protein Kinases / drug effects
  • Protein Kinases / genetics
  • Protein Kinases / immunology*
  • Salmonella typhimurium / enzymology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / immunology*
  • Signal Transduction / immunology
  • Time Factors
  • Transcription, Genetic / genetics

Substances

  • Antimicrobial Cationic Peptides
  • Bacterial Proteins
  • PhoQ protein, Bacteria
  • Protein Kinases
  • Magnesium

Associated data

  • PDB/1YAX