title: Signal transduction by a death signal peptide: uncovering the mechanism of bacterial killing by penicillin.
abstract: 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.
authors.affiliation: St. Jude Children's Research Hospital, Department for Infectious Diseases, Memphis, Tennessee 38105, USA.
authors.forename: R
authors.initials: R
authors.lastname: Novak
authors.forename: E
authors.initials: E
authors.lastname: Charpentier
authors.forename: J S
authors.initials: JS
authors.lastname: Braun
authors.forename: E
authors.initials: E
authors.lastname: Tuomanen
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D008969:Molecular Sequence Data; D010406:Penicillins / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D021382:Protein Sorting Signals / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D010406:Penicillins; D021382:Protein Sorting Signals; D014157:Transcription Factors; C119633:VncR protein, Streptococcus pneumoniae; D014640:Vancomycin; D011494:Protein Kinases; C119671:VncS histidine kinase