Antimicrobial Peptides Activate the Vibrio Cholerae sigmaE Regulon Through an OmpU-dependent Signalling Pathway

Mol Microbiol. 2007 Feb;63(3):848-58. doi: 10.1111/j.1365-2958.2006.05544.x. Epub 2006 Dec 20.

Abstract

Vibrio cholerae, an enteric pathogen, is subject to assault by several membrane-acting, host gut-derived antimicrobial peptides (AP). We previously found that a major V. cholerae outer membrane protein, OmpU, confers resistance to polymyxin B and to a bioactive peptide (P2) derived from the human bactericidal/permeability-increasing protein. Here, we report that the alternative sigma factor sigma(E) also plays a critical role in determining V. cholerae resistance to AP and that OmpU and sigma(E) lie in the same pathway. In fact, we found that OmpU is a key determinant of basal sigma(E) expression. We also found that sublethal AP exposure activates sigma(E) and the sigma(E)-mediated periplasmic stress response. sigma(E) is not activated by P2 in V. cholerae cells lacking OmpU or DegS, a periplasmic protease that controls sigma(E) activity. The lack of AP-elicited sigma(E) activation in a strain harbouring a point mutation in OmpU's putative DegS-binding residues provides support for a link between OmpU and DegS-mediated activation of sigma(E). We propose that AP-induced membrane perturbations change the conformation of OmpU to trigger a DegS-dependent sigma(E)-activating cascade. Thus, OmpU appears to act as a sensor component in a signal transduction pathway.

Publication types

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

MeSH terms

  • Adhesins, Bacterial / chemistry
  • Adhesins, Bacterial / metabolism*
  • Amino Acid Motifs
  • Antimicrobial Cationic Peptides / metabolism
  • Antimicrobial Cationic Peptides / pharmacology*
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / metabolism*
  • Bacterial Proteins / metabolism
  • Blood Proteins / metabolism
  • Blood Proteins / pharmacology*
  • Humans
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Regulon*
  • Sigma Factor / metabolism*
  • Signal Transduction*
  • Transcription Factors / metabolism*
  • Vibrio cholerae / genetics*
  • Vibrio cholerae / immunology
  • Vibrio cholerae / metabolism

Substances

  • Adhesins, Bacterial
  • Antimicrobial Cationic Peptides
  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Blood Proteins
  • DegS protein, Bacteria
  • Membrane Proteins
  • OmpU protein, Vibrio cholerae
  • Peptide Fragments
  • Sigma Factor
  • Transcription Factors
  • bactericidal permeability increasing protein
  • sporulation-specific sigma factors