Signal transduction by a death signal peptide: uncovering the mechanism of bacterial killing by penicillin

Mol Cell. 2000 Jan;5(1):49-57. doi: 10.1016/s1097-2765(00)80402-5.


The binding of bactericidal antibiotics like penicillins, cephalosporins, and glycopeptides to their bacterial targets stops bacterial growth but does not directly cause cell death. A second process arising from the bacteria itself is necessary to trigger endogenous suicidal enzymes that dissolve the cell wall during autolysis. The signal and the trigger pathway for this event are completely unknown. Using S. pneumoniae as a model, we demonstrate that signal transduction via the two-component system VncR/S triggers multiple death pathways. We show that the signal sensed by VncR/S is a secreted peptide, Pep27, that initiates the cell death program. These data depict a novel model for the control of bacterial cell death.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Microbial Sensitivity Tests
  • Models, Biological
  • Molecular Sequence Data
  • Penicillins / pharmacology*
  • Protein Kinases / genetics
  • Protein Kinases / physiology*
  • Protein Sorting Signals / chemistry
  • Protein Sorting Signals / genetics
  • Protein Sorting Signals / physiology*
  • Streptococcus pneumoniae / cytology
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / physiology*
  • Subcellular Fractions / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Vancomycin / pharmacology


  • Bacterial Proteins
  • Penicillins
  • Protein Sorting Signals
  • Transcription Factors
  • VncR protein, Streptococcus pneumoniae
  • Vancomycin
  • Protein Kinases
  • VncS histidine kinase

Associated data

  • GENBANK/AF140784