Editors' ChoiceBacteriology

Death Signal Cascade in Bacteria

Science's STKE  08 Feb 2000:
Vol. 2000, Issue 18, pp. tw3
DOI: 10.1126/stke.2000.18.tw3

The bacterial cell wall is the target for many antibiotics, which deregulate the extracellular autolytic enzymes leading to cell death. Novak et al. screened a library of loss-of-function mutants for penicillin tolerance in order to discover genes that are responsible for regulating bacterial autolysis. A two-component signaling system, VncR/S, was discovered along with a 27-amino acid peptide, Pep27, and an ABC transporter, Vex. Their data show that synthetic Pep27 was bactericidal even to cells deficient in the major autolysin, but the bactericidal property was dependent on functional VncS. Secretion of endogenous Pep27 and detection by the VncR/S system was important for antibiotic-mediated cell death. Cells with disrupted pep27 and vex genes or disrupted vncS were tolerant to a broad range of antibiotics. Detection of Pep27 by the VncS histidine phosphatase regulates the phosphorylation state of VncR, which regulates the cell death pathways.

Novak, R., Charpentier, E., Braun, J.S., Tuomanen, E. (2000) Signal transduction by a death signal peptide: Uncovering the mechanism of bacterial killing by penicillin. Mol. Cell 5: 49-57. [Online Journal]