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


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.

Download full-text


Available from: Hanna Engelberg-Kulka, Oct 28, 2014
  • Source
    • "Recently, the antibacterial mechanism of Ag NPs has only been partially elucidated. Programmed cell death (PCD), which causes apoptosis, is an essential mechanism in eukaryotic organisms (Erental et al., 2012) and also can be found in prokaryotic cells, such as Escherichia coli cells (Dwyer and Winkler, 2013). Inhibition of new DNA formation in the cells is positively correleated with concentration (Bao et al., 2015). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The current study sought to explore the response of application of purified silver nanoparticles (Ag NPs) to soil grown with faba bean (Vicia faba L.) and inoculated either with Rhizobium leguminosarum bv. viciae ASU (KF670819) or Glomus aggregatum 14G or in combination. Ag NPs was synthesized and stabilized using PVP and characterized by UV-vis spectroscopy and the characteristic surface plasmon resonance band centered at 430nm. Also, the morphologies and structures of Ag NPs were characterized by X-ray diffraction and transmission electron microscopy and the size distribution ranged from 5 to 50nm. In the first experiment, the germination and seedling growth of faba bean plants were tested under different concentrations of Ag+ as AgNO3 and Ag NPs (100-900μgkg-1 soil). The germination declined by 40% when exposed to Ag NPs at concentration 800μgkg-1 soil, while the same level from Ag+ completely inhibited seed germination. In the second experiment the effect of a high concentration of Ag NPs (800μgkg-1 soil) on R. leguminosarum bv. viciae growth and G. aggregatum activity in soil and their symbiosis with faba bean was investigated. It was proved that Ag NPs considerably retarded the process of nodulation, nitrogenase activity, mycorrhizal colonization, mycorrhizal responsiveness and glomalin content. High concentration of Ag NPs (800μgkg-1 soil) resulted in detectable alterations including the intracellular deterioration of cytoplasmic components by means of autophagy and disintegration of bacteroids. These findings elucidate the mechanism of toxic action of Ag NPs which resulted in early senescence of root nodules.
    Full-text · Article · Feb 2016 · Agriculture Ecosystems & Environment
  • Source
    • "While the role of plasmid-encoded TA systems as addictive modules has been extensively studied (Gerdes et al., 1986;Yarmolinsky, 1995;Engelberg-Kulka and Glaser, 1999;Cooper and Heinemann, 2000;Patel and Weaver, 2006), the physiological importance of chromosomally encoded TA systems is still under debate. A possible involvement in the following mechanisms has been proposed: (i) growth modulation under stress (Gerdes, 2000;Christensen et al., 2003;Gerdes et al., 2005); (ii) generation of persister cells (Maisonneuve et al., 2011, Gerdes and Maisonneuve, 2012); (iii) genome maintenance (Szekeres et al., 2007); and (iv) programmed cell death (Kulka and Glaser, 1999;Hazan et al., 2004;Mutschler et al., 2011;Erental et al., 2012). An additional hypothesized role, which relates to TA modules found in pathogenic bacteria, suggests that these systems may be involved in growth regulation of bacteria once inside the host cells (Hopper et al., 2000;Ren et al., 2012;De la Cruz et al., 2013). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Toxin–antitoxin systems are commonly found on plasmids and chromosomes of bacteria and archaea. These systems appear as biscystronic genes encoding a stable toxin and a labile antitoxin, which protects the cells from the toxin’s activity. Under specific, mostly stressful conditions, the unstable antitoxin is degraded, the toxin becomes active and growth is arrested. Using genome analysis we identified a putative toxin–antitoxin encoding system in the genome of the plant pathogen Acidovorax citrulli. The system is homologous to vapB-vapC systems from other bacterial species. PCR and phylogenetic analyses suggested that this locus is unique to group II strains of A. citrulli. Using biochemical and molecular analyses we show that A. citrulli VapBC module is a bona- fide toxin–antitoxin module in which VapC is a toxin with ribonuclease activity that can be counteracted by its cognate VapB antitoxin. We further show that the transcription of A. citrulli vapBC locus is induced by amino acid starvation, chloramphenicol and during plant infection. Due to the possible role of TA systems in both virulence and dormancy of human pathogenic bacteria, studies of these systems are gaining a lot of attention. Conversely, studies characterizing toxin–antitoxin systems in plant pathogenic bacteria are lacking. The study presented here validates the activity of VapB and VapC proteins in A. citrulli and suggests their involvement in stress response and host-pathogen interactions.
    Full-text · Article · Jan 2016 · Frontiers in Microbiology
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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.
    Full-text · Article · Feb 2015 · Molecular Microbiology
Show more