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J Bacteriol. 2008 May;190(9):3169-75. doi: 10.1128/JB.01918-07. Epub 2008 Feb 29.

The extracellular death factor: physiological and genetic factors influencing its production and response in Escherichia coli.

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  • 1Department of Molecular Biology, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.


Gene pairs specific for a toxin and its antitoxin are called toxin-antitoxin modules and are found on the chromosomes of many bacteria. The most studied of these modules is Escherichia coli mazEF, in which mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. In a previous report from this laboratory, it was shown that mazEF-mediated cell death is a population phenomenon requiring a quorum-sensing peptide called the extracellular death factor (EDF). EDF is the linear pentapeptide NNWNN (32). Here, we further confirm that EDF is a signal molecule in a mixed population. In addition, we characterize some physiological conditions and genes required for EDF production and response. Furthermore, stress response and the gene specifying MazEF, the Zwf (glucose-6-phosphate dehydrogenase) gene, and the protease ClpXP are critical in EDF production. Significant strain differences in EDF production and response explain variations in the induction of mazEF-mediated cell death.

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