scholarly journals Programmed Cell Death in Escherichia coli: Some Antibiotics Can Trigger mazEFLethality

2001 ◽  
Vol 183 (6) ◽  
pp. 2041-2045 ◽  
Author(s):  
Boaz Sat ◽  
Ronen Hazan ◽  
Tova Fisher ◽  
Hanita Khaner ◽  
Gad Glaser ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Bacterial Chromosome ◽  
E Coli ◽  
Bacterial Cultures ◽  
Gene Pairs ◽  
System A ◽  
Extrachromosomal Elements

ABSTRACT The discovery of toxin-antitoxin gene pairs (also called addiction modules) on extrachromosomal elements of Escherichia coli, and particularly the discovery of homologous modules on the bacterial chromosome, suggest that a potential for programmed cell death may be inherent in bacterial cultures. We have reported on the E. coli mazEF system, a regulatable addiction module located on the bacterial chromosome. MazF is a stable toxin and MazE is a labile antitoxin. Here we show that cell death mediated by the E. coli mazEF module can be triggered by several antibiotics (rifampicin, chloramphenicol, and spectinomycin) that are general inhibitors of transcription and/or translation. These antibiotics inhibit the continuous expression of the labile antitoxin MazE, and as a result, the stable toxin MazF causes cell death. Our results have implications for the possible mode(s) of action of this group of antibiotics.

scholarly journals The Escherichia coli mazEF Suicide Module Mediates Thymineless Death

2003 ◽  
Vol 185 (6) ◽  
pp. 1803-1807 ◽  
Author(s):  
Boaz Sat ◽  
Myriam Reches ◽  
Hanna Engelberg-Kulka
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Molecular Mechanism ◽  
Stress Conditions ◽  
E Coli ◽  
System A ◽  
Thymine Starvation ◽  
Thymineless Death

ABSTRACT In 1954, Cohen and Barner discovered that a thymine auxotrophic (thyA) mutant of Escherichia coli undergoes cell death in response to thymine starvation. This phenomenon, called thymineless death (TLD), has also been found in many other organisms, including prokaryotes and eukaryotes. Though TLD has been studied intensively, its molecular mechanism has not yet been explained. Previously we reported on the E. coli mazEF system, a regulatable chromosomal suicide module that can be triggered by various stress conditions. MazF is a stable toxin, and MazE is an unstable antitoxin. Here, we show that cell death that is mediated by the mazEF module can also be activated by thymine starvation. We found that TLD depends on E. coli mazEF and that under thymine starvation, the activity of the mazEF promoter P2 is significantly reduced. Our results, which describe thymine starvation as a trigger for a built-in death program, have implications for programmed cell death in both prokaryotes and eukaryotes.

scholarly journals MazF-Mediated Cell Death in Escherichia coli: a Point of No Return

2004 ◽  
Vol 186 (24) ◽  
pp. 8295-8300 ◽  
Author(s):  
Shahar Amitai ◽  
Yussuf Yassin ◽  
Hanna Engelberg-Kulka
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Inhibitory Effect ◽  
Luria Bertani ◽  
E Coli ◽  
Ectopic Overexpression ◽  
Point Of No Return ◽  
The Rich ◽  
Overexpression System

ABSTRACT mazEF is a stress-induced toxin-antitoxin module, located on the chromosome of Escherichia coli, that we have previously described to be responsible for programmed cell death in E. coli. mazF specifies a stable toxin, and mazE specifies a labile antitoxin. Recently, it was reported that inhibition of translation and cell growth by ectopic overexpression of the toxin MazF can be reversed by the action of the antitoxin MazE ectopically overexpressed at a later time. Based on these results, it was suggested that rather than inducing cell death, mazF induces a state of reversible bacteriostasis (K. Pederson, S. K. Christensen, and K. Gerdes, Mol. Microbiol. 45:501-510, 2002). Using a similar ectopic overexpression system, we show here that overexpression of MazE could reverse MazF lethality only over a short window of time. The size of that window depended on the nature of the medium in which MazF was overexpressed. Thus, we found “a point of no return,” which occurred sooner in minimal M9 medium than it did in the rich Luria-Bertani medium. We also describe a state in which the effect of MazF on translation could be separated from its effect on cell death: MazE overproduction could completely reverse the inhibitory effect of MazF on translation, while not affecting the bacteriocidic effect of MazF at all. Our results reported here support our view that the mazEF module mediates cell death and is part of a programmed cell death network.

scholarly journals Postsegregational Killing Mediated by the P1 Phage “Addiction Module” phd-doc Requires the Escherichia coli Programmed Cell Death SystemmazEF

2001 ◽  
Vol 183 (6) ◽  
pp. 2046-2050 ◽  
Author(s):  
Ronen Hazan ◽  
Boaz Sat ◽  
Myriam Reches ◽  
Hanna Engelberg-Kulka
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Protein Synthesis ◽  
Programmed Cell Death ◽  
Killing Effect ◽  
E Coli ◽  
Lethal Action ◽  
Free Cells ◽  
Postsegregational Killing

ABSTRACT “Addiction modules” consist of two genes; the product of the second is long lived and toxic, while the product of the first is short lived and antagonizes the lethal action of the toxin. The extrachromosomal addiction module phd-doc, located on the P1 prophage, is responsible for the postsegregational killing effect (death of plasmid-free cells). The Escherichia colichromosomal addiction module analogue, mazEF, is responsible for the induction of programmed cell death. Here we show that the postsegregational killing mediated by the P1phd-doc module depends on the presence of the E. coli mazEF system. In addition, we demonstrate that under conditions of postsegregational killing, mediated byphd-doc, protein synthesis of E. coli is inhibited. Based on our findings, we suggest the existence of a coupling between the phd-doc and mazEFsystems.

scholarly journals “mazEFmediated programmed cell death in Escherichia coli”: is it?

2016 ◽  
Author(s):  
Bhaskar Chandra Mohan Ramisetty ◽  
Swati Raj ◽  
Dimpy Ghosh
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Stress Tolerance ◽  
Type Ii ◽  
Overlapping Genes ◽  
Wild Type ◽  
E Coli ◽  
Typical Type ◽  
Metabolic Fitness

AbstractToxin-antitoxins systems (TAS) are prokaryotic operons containing two small overlapping genes which encode two components referred to as Toxin and Antitoxin. Involvement of TAS in bacterial programmed cell death (PCD) is highly controversial. MazEF, a typical type II TAS, is particularly implicated in mediating PCD inEscherichia coli. Hence, we compared the metabolic fitness and stress tolerance ofE. colistrains (MC4100 and itsmazEF- derivative) which were extensively used by proponents ofmazEF- mediated PCD. We found that both the strains are deficient inrelAgene and that theΔmazEFstrain has lower fitness and stress tolerance compared to wild type MC4100. Furthermore, these strains are likely not isogenic. We could not reproducemazEFmediated PCD which emphasizes the need for skeptic approach to the PCD hypothesis.

scholarly journals Escherichia coli K12 Upregulates Programmed Cell Death Ligand 1 (PD-L1) Expression in Gamma Interferon-Sensitized Intestinal Epithelial Cells via the NF-κB Pathway

2020 ◽  
Vol 89 (1) ◽  
pp. e00618-20 ◽  
Author(s):  
Seul A. Lee ◽  
Yiming Wang ◽  
Fang Liu ◽  
Stephen M. Riordan ◽  
Lu Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Bacterial Species ◽  
Intestinal Epithelial ◽  
Content Type ◽  
E Coli ◽  
Inflammatory Conditions ◽  
Ifn Γ ◽  
Ht 29

ABSTRACTProgrammed cell death ligand-1 (PD-L1) is an immune checkpoint protein which is used by tumor cells for immune evasion. PD-L1 is upregulated in inflamed intestinal tissues. The intestinal tract is colonized by millions of bacteria, most of which are commensal bacterial species. We hypothesized that under inflammatory conditions, some commensal bacterial species contribute to increased PD-L1 expression in intestinal epithelium and examined this hypothesis. Human intestinal epithelial HT-29 cells with and without interferon (IFN)-γ sensitization were incubated with six strains of four enteric bacterial species. The mRNA and protein levels of PD-L1 in HT-29 cells were examined using quantitative real-time PCR and flow cytometry, respectively. The levels of interleukin (IL)-1β, IL-18, IL-6, IL-8, and tumor necrosis factor (TNF)-α secreted by HT-29 cells were measured using enzyme-linked immunosorbent assay. Apoptosis of HT-29 cells was measured using a caspase 3/7 assay. We found that Escherichia coli K12 significantly upregulated both PD-L1 mRNA and protein in IFN-γ-sensitized HT-29 cells. E. coli K12 induced the production of IL-8 in HT-29 cells, however, IL-8 did not affect HT-29 PD-L1 expression. Inhibition of the nuclear factor-kappa B pathway significantly reduced E. coli K12-induced PD-L1 expression in HT-29 cells. The other two E. coli strains and two enteric bacterial species did not significantly affect PD-L1 expression in HT-29 cells. Enterococcus faecalis significantly inhibited PD-L1 expression due to induction of cell death. Data from this study suggest that some gut bacterial species have the potential to affect immune function under inflammatory conditions via upregulating epithelial PD-L1 expression.

scholarly journals Induction of Escherichia coli Chromosomal mazEF by Stressful Conditions Causes an Irreversible Loss of Viability

2006 ◽  
Vol 188 (9) ◽  
pp. 3420-3423 ◽  
Author(s):  
Ilana Kolodkin-Gal ◽  
Hanna Engelberg-Kulka
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Basic Characteristic ◽  
Irreversible Loss ◽  
Previous Conclusion ◽  
E Coli ◽  
Programmed Death

ABSTRACT mazEF is a stress-induced toxin-antitoxin module located on the chromosomes of many bacteria. Here we induced Escherichia coli chromosomal mazEF by various stressful conditions. We found an irreversible loss of viability, which is the basic characteristic of cell death. These results further support our previous conclusion that E. coli mazEF mediation of cell death is not a passive process, but an active and genetically “programmed” death response.

Expression of Psychrophilic Genes in Mesophilic Hosts: Assessment of the Folding State of a Recombinant α-Amylase

1998 ◽  
Vol 64 (3) ◽  
pp. 1163-1165 ◽  
Author(s):  
Georges Feller ◽  
Olivier Le Bussy ◽  
Charles Gerday
Keyword(s):  
Escherichia Coli ◽  
Enzyme Stability ◽  
Expression System ◽  
Wild Strain ◽  
Culture Temperature ◽  
E Coli ◽  
System A ◽  
Irreversible Denaturation ◽  
The Antarctic ◽  
Folding State

ABSTRACT α-Amylase from the antarctic psychrophile Alteromonas haloplanktis is synthesized at 0 ± 2°C by the wild strain. This heat-labile α-amylase folds correctly when overexpressed in Escherichia coli, providing the culture temperature is sufficiently low to avoid irreversible denaturation. In the described expression system, a compromise between enzyme stability and E. coli growth rate is reached at 18°C.

Nanomolar Levels of Dimethylsulfoniopropionate, Dimethylsulfonioacetate, and Glycine Betaine Are Sufficient To Confer Osmoprotection to Escherichia coli

1999 ◽  
Vol 65 (8) ◽  
pp. 3304-3311 ◽  
Author(s):  
Anne Cosquer ◽  
Vianney Pichereau ◽  
Jean-Alain Pocard ◽  
Jacques Minet ◽  
Michel Cormier ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Salinity Tolerance ◽  
Glycine Betaine ◽  
Standard Laboratory ◽  
E Coli ◽  
High Affinity ◽  
Bacterial Cultures ◽  
Transport Studies ◽  
Ecological Implications ◽  
Substrate Concentrations

ABSTRACT We combined the use of low inoculation titers (300 ± 100 CFU/ml) and enumeration of culturable cells to measure the osmoprotective potentialities of dimethylsulfoniopropionate (DMSP), dimethylsulfonioacetate (DMSA), and glycine betaine (GB) for salt-stressed cultures of Escherichia coli. Dilute bacterial cultures were grown with osmoprotectant concentrations that encompassed the nanomolar levels of GB and DMSP found in nature and the millimolar levels of osmoprotectants used in standard laboratory osmoprotection bioassays. Nanomolar concentrations of DMSA, DMSP, and GB were sufficient to enhance the salinity tolerance of E. coli cells expressing only the ProU high-affinity general osmoporter. In contrast, nanomolar levels of osmoprotectants were ineffective with a mutant strain (GM50) that expressed only the low-affinity ProP osmoporter. Transport studies showed that DMSA and DMSP, like GB, were taken up via both ProU and ProP. Moreover, ProU displayed higher affinities for the three osmoprotectants than ProP displayed, and ProP, like ProU, displayed much higher affinities for GB and DMSA than for DMSP. Interestingly, ProP did not operate at substrate concentrations of 200 nM or less, whereas ProU operated at concentrations ranging from 1 nM to millimolar levels. Consequently,proU + strains of E. coli, but not the proP + strain GM50, could also scavenge nanomolar levels of GB, DMSA, and DMSP from oligotrophic seawater. The physiological and ecological implications of these observations are discussed.

scholarly journals A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in Escherichia coli

mBio ◽  
2015 ◽  
Vol 6 (6) ◽  
Author(s):  
Liselot Dewachter ◽  
Natalie Verstraeten ◽  
Daniel Monteyne ◽  
Cyrielle Ines Kint ◽  
Wim Versées ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Surface ◽  
Single Amino Acid ◽  
Altruistic Behavior ◽  
Membrane Blebbing ◽  
Cell Death Pathway ◽  
Higher Eukaryotes ◽  
Multicellular Organisms

ABSTRACT Programmed cell death (PCD) is an important hallmark of multicellular organisms. Cells self-destruct through a regulated series of events for the benefit of the organism as a whole. The existence of PCD in bacteria has long been controversial due to the widely held belief that only multicellular organisms would profit from this kind of altruistic behavior at the cellular level. However, over the past decade, compelling experimental evidence has established the existence of such pathways in bacteria. Here, we report that expression of a mutant isoform of the essential GTPase ObgE causes rapid loss of viability in Escherichia coli. The physiological changes that occur upon expression of this mutant protein—including loss of membrane potential, chromosome condensation and fragmentation, exposure of phosphatidylserine on the cell surface, and membrane blebbing—point to a PCD mechanism. Importantly, key regulators and executioners of known bacterial PCD pathways were shown not to influence this cell death program. Collectively, our results suggest that the cell death pathway described in this work constitutes a new mode of bacterial PCD. IMPORTANCE Programmed cell death (PCD) is a well-known phenomenon in higher eukaryotes. In these organisms, PCD is essential for embryonic development—for example, the disappearance of the interdigital web—and also functions in tissue homeostasis and elimination of pathogen-invaded cells. The existence of PCD mechanisms in unicellular organisms like bacteria, on the other hand, has only recently begun to be recognized. We here demonstrate the existence of a bacterial PCD pathway that induces characteristics that are strikingly reminiscent of eukaryotic apoptosis, such as fragmentation of DNA, exposure of phosphatidylserine on the cell surface, and membrane blebbing. Our results can provide more insight into the mechanism and evolution of PCD pathways in higher eukaryotes. More importantly, especially in the light of the looming antibiotic crisis, they may point to a bacterial Achilles’ heel and can inspire innovative ways of combating bacterial infections, directed at the targeted activation of PCD pathways.

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