Two Programmed Cell Death Systems in Escherichia coli: An Apoptotic-Like Death Is Inhibited by the mazEF-Mediated Death Pathway

Abstract

Author SummaryThe enteric bacterium Escherichia coli, like most other bacteria, carries on its chromosome a pair of genes, mazE and mazF (mazEF): mazF specifies a toxin, and mazE specifies an antitoxin. Previously, we have shown that E. coli mazEF is responsible for bacterial programmed cell death in response to stressors such as DNA damage. Here, we report that extensive DNA damage can induce a second mode of cell death, which we call apoptotic-like death (ALD). ALD is like apoptosis—a mode of cell death that has previously been recorded only in eukaryotes. During ALD, the cell membrane is depolarized, and the DNA is fragmented and can be detected using the classical TUNEL assay. The MazEF death pathway, however, shows neither of those features, yet also kills the cell. We show that ALD is mediated by two proteins, RecA and LexA, which are noteworthy because LexA is an inhibitor of the SOS response (which is a global response to DNA damage in which the cell cycle is arrested and DNA repair is induced). This defines ALD as a form of SOS response. Furthermore, MazEF and its downstream components cause reduction of recA mRNA levels, which could explain how the MazEF pathway inhibits the ALD pathway. We conclude that the E. coli ALD pathway is a back-up system for the traditional mazEF cell death pathway. Should one of the components of the mazEF pathway be inactivated, bacterial cell death would occur through ALD. These findings also have implications for the mechanisms of “altruistic” cell death among bacterial populations.