Regulation of Salmonella Typhimurium Virulence Gene Expression by Cationic Antimicrobial Peptides

Mol Microbiol. 2003 Oct;50(1):219-30. doi: 10.1046/j.1365-2958.2003.03675.x.

Abstract

Cationic antimicrobial peptides (CAMP) represent a conserved and highly effective component of innate immunity. During infection, the Gram-negative pathogen Salmonella typhimurium induces different mechanisms of CAMP resistance that promote pathogenesis in animals. This study shows that exposure of S. typhimurium to sublethal concentrations of CAMP activates the PhoP/PhoQ and RpoS virulence regulons, while repressing the transcription of genes required for flagella synthesis and the invasion-associated type III secretion system. We further demonstrate that growth of S. typhimurium in low doses of the alpha-helical peptide C18G induces resistance to CAMP of different structural classes. Inducible resistance depends on the presence of PhoP, indicating that the PhoP/PhoQ system can sense sublethal concentrations of cationic antimicrobial peptides. Growth of S. typhimurium in the presence of CAMP also leads to RpoS-dependent protection against hydrogen peroxide. Because bacterial resistance to oxidative stress and CAMP are induced during infection of animals, CAMP may be an important signal recognized by bacteria on colonization of animal tissues.

Publication types

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

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial*
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression Profiling
  • Gene Expression Regulation, Bacterial / drug effects*
  • Genes, Bacterial
  • Genes, Reporter / genetics
  • Oxidative Stress / genetics
  • Peptide Mapping
  • Polymyxins / metabolism
  • Polymyxins / pharmacology
  • Proteome / analysis
  • Regulon / physiology
  • Salmonella typhimurium / drug effects
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / pathogenicity*
  • Sigma Factor / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Virulence / genetics*
  • beta-Galactosidase / metabolism

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Bacterial Proteins
  • PhoQ protein, Bacteria
  • Polymyxins
  • Proteome
  • Sigma Factor
  • sigma factor KatF protein, Bacteria
  • PhoP protein, Bacteria
  • Alkaline Phosphatase
  • beta-Galactosidase