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

Baylor College of Medicine, United States of America
PLoS Biology (Impact Factor: 9.34). 03/2012; 10(3):e1001281. DOI: 10.1371/journal.pbio.1001281
Source: PubMed

ABSTRACT Author Summary
The 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.

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Available from: Hanna Engelberg-Kulka, Oct 28, 2014
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    • "In the absence of ClpPA activity, the MazE antitoxin remains intact and antagonizes the activity of the MazF toxin (Engelberg-Kulka et al., 1998). In the absence of MazF activity, when the cells are subjected to conditions causing DNA damage, the recA-lexA-mediated SOS response takes place (Erental et al., 2012; 2014). The action of the SOS response leads to the degradation of the λ repressor cI, resulting in the phage switching from its lysogenic to lytic cycle and the eventual lysis of the host cell (Kalderon et al., 2014). "
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    ABSTRACT: The life cycle of phage λ has been studied extensively. Of particular interest has been the process leading to the decision of the phage to switch from lysogenic to lytic cycle. The principal participant in this process is the λcI repressor, which is cleaved under conditions of DNA damage. Cleaved λcI no longer acts as a repressor, allowing phage λ to switch from its lysogenic to lytic cycle. The well known mechanism responsible for λcI cleavage is the SOS response. We have recently reported that the E. coli toxin-antitoxin mazEF pathway inhibits the SOS response; in fact, the SOS response is permitted only in E. coli strains deficient in the expression of the mazEF pathway. Moreover, in strains lysogenic for prophage λ, the SOS response is enabled by the presence of λrexB. λRexB had previously been found to inhibit the degradation of the antitoxin MazE, thereby preventing the toxic action of MazF. Thus, phage λ rexB gene not only safeguards the prophage state by preventing death of its E.coli host, but is also indirectly involved in the lysogenic-lytic switch. This article is protected by copyright. All rights reserved.
    Molecular Microbiology 02/2015; 96(4). DOI:10.1111/mmi.12969 · 4.42 Impact Factor
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    • "MazEF-like modules have been shown to occur on the chromosomes of many bacteria [51]. Erental and colleagues [53] report that, in E. coli, MazEF-mediated cell death is induced by a quorum-sensing factor (the extracellular death factor) which induces the endoribonucleolytic activity of MazF. Although the MazEF death pathway does not show the major features of apoptosis, these authors also describe an apoptosis-like death pathway in which the membrane is depolarized and DNA is fragmented. "
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    ABSTRACT: It is more than 25 years since the first report that a protozoan parasite could die by a process resulting in a morphological phenotype akin to apoptosis. Since then these phenotypes have been observed in many unicellular parasites, including trypanosomatids and apicomplexans, and experimental evidence concerning the molecular pathways that are involved is growing. These observations support the view that this form of programmed cell death is an ancient one that predates the evolution of multicellularity. Here we review various hypotheses that attempt to explain the origin of apoptosis, and look for support for these hypotheses amongst the parasitic protists as, with the exception of yeast, most of the work on death mechanisms in unicellular organisms has focussed on them. We examine the role that addiction modules may have played in the original eukaryote cell and the part played by mitochondria in the execution of present day cells, looking for examples from Leishmania spp. Trypanosoma spp. and Plasmodium spp. In addition, the expanding knowledge of proteases, nucleases and other molecules acting in protist execution pathways has enabled comparisons to be made with extant Archaea and bacteria and with biochemical pathways that evolved in metazoans. These comparisons lend support to the original sin hypothesis but also suggest that present-day death pathways may have had multifaceted beginnings.
    Parasites & Vectors 04/2013; 6(1):108. DOI:10.1186/1756-3305-6-108 · 3.43 Impact Factor
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    • "One common successful survival strategy is the ability to undergo reversible growth arrest observed in almost all prokaryotes [3], [4]. The roles of chromosomal toxin-antitoxin (TA) systems in regulation of bacterial growth is such a good example, which have been documented in many organisms, especially Escherichia coli, to cope with various stresses by reducing growth, inhibiting growth or killing a subpopulation of cells [5]–[8]. However, based on the authors' best knowledge there is no similar report in cyanobacteria so far. "
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    ABSTRACT: Cyanobacteria have evolved to survive stressful environmental changes by regulating growth, however, the underlying mechanism for this is obscure. The ability of chromosomal type II toxin-antitoxin (TA) systems to modulate growth or cell death has been documented in a variety of prokaryotes. A chromosomal locus of sp. PCC 7120 has been predicted as a putative TA system. Here we demonstrate that form a bicistronic operon that is co-transcribed under normal growth conditions. Overproduction of MazFa induced growth arrest which could be neutralized by co-expression of MazEa. MazFa also inhibited the growth of cells, and this effect could be overcome by simultaneous or subsequent expression of MazEa via formation of the MazEa-MazFa complex , further confirming the nature of the locus as a type II TA system. Interestingly, like most TA systems, deletion of had no effect on the growth of during the tested stresses. Our data suggest that , or together with other chromosomal type II TA systems, may promote cells to cope with particular stresses by inducing reversible growth arrest of .
    PLoS ONE 02/2013; 8(2):e56035. DOI:10.1371/journal.pone.0056035 · 3.23 Impact Factor
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