Antimicrobial peptides activate the Vibrio cholerae sigmaE regulon through an OmpU-dependent signalling pathway.
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.
Mathur
Jyoti
J
Program in Immunology, Tufts University and Howard Hughes Medical Institute, 136 Harrison Avenue, Boston, MA 02111, USA.
Davis
Brigid M
BM
Waldor
Matthew K
MK
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D018085:Regulon; D012808:Sigma Factor / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014734:Vibrio cholerae / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D018829:Adhesins, Bacterial; D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001798:Blood Proteins; C066496:DegS protein, Bacteria; D008565:Membrane Proteins; C096349:OmpU protein, Vibrio cholerae; D010446:Peptide Fragments; D012808:Sigma Factor; D014157:Transcription Factors; C021623:bactericidal permeability increasing protein; C063202:sporulation-specific sigma factors