The alternative sigma factor sigma is required for resistance of Salmonella enterica serovar Typhimurium to anti-microbial peptides

Mol Microbiol. 2005 May;56(3):789-99. doi: 10.1111/j.1365-2958.2005.04578.x.

Abstract

The enteric pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters a variety of anti-microbial peptides during the course of infection. We report here that the extracytoplasmic sigma factor sigma(E) (RpoE) is required for Salmonella resistance to killing by the bactericidal/permeability-increasing protein (BPI)-derived peptide P2 and the murine alpha-defensin cryptdin-4 (Crp4). Moreover, sigma(E)-deficient S. Typhimurium is attenuated for virulence after oral infection of immunocompromised gp91phox(-/-) mice that lack a functional NADPH phagocyte oxidase, suggesting that sigma(E) plays an important role in resistance to non-oxidative mucosal host defences such as anti-microbial peptides. Although both P2 and Crp4 target the cell envelope, bacterial killing by these peptides appears to occur by distinct mechanisms. Formate enhances bacterial resistance to P2, as previously demonstrated, but not to Crp4. Both sigma(E) and cytoplasmic membrane-associated formate dehydrogenase are required for the protective effect of formate against P2. In contrast to P2, Crp4 does not inhibit bacterial respiration at lethal concentrations. However, both peptides induce expression of rpoE, suggesting that they trigger a common mechanism for sensing extracytoplasmic stress.

Publication types

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

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Cytoplasm / metabolism
  • Drug Resistance, Bacterial / physiology*
  • Formates / pharmacology
  • Gene Expression Regulation, Bacterial / drug effects
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microbial Sensitivity Tests
  • Mutation
  • NADPH Oxidase 2
  • NADPH Oxidases / genetics
  • Oxygen / metabolism
  • Peptide Fragments / pharmacology
  • Salmonella Infections, Animal / drug therapy
  • Salmonella Infections, Animal / microbiology
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / pathogenicity
  • Salmonella typhimurium / physiology*
  • Sigma Factor / drug effects
  • Sigma Factor / genetics
  • Sigma Factor / metabolism*
  • Transcription Factors / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Virulence
  • alpha-Defensins / pharmacology

Substances

  • Anti-Bacterial Agents
  • Formates
  • Membrane Glycoproteins
  • Membrane Proteins
  • Peptide Fragments
  • Sigma Factor
  • Transcription Factors
  • alpha-Defensins
  • cryptdin 4, mouse
  • endotoxin binding proteins
  • sporulation-specific sigma factors
  • formic acid
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases
  • Oxygen