The response of E.coli under mild stress and intolerable stress condition. The genes in the are worked on toxin and antitoxin induced and inhibition mechanism after the SOS response activation in cell.i In that apoptosis the PCD activation start after the SOS activation of cell.SOS( save our soul,it US army code for rescue) that means intolerable stress and preserve the DNA other proteins for spore formation and reuse the material. after the DNA preservation the cell lysis takes place and cell get died and autophagy occur. IN presentation the difference between the prokaryotic and eukaryotic cell also shown. In this the E.coli shown apoptotic like death (ALD) and genes are active during the programmed cell death (PCD)conditions. the genes which are switched off and on at time apoptosis is mention in presentation

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APOPTOSIS –
THE PROGRAMMED CELL
DEATH
SUBMITTED TO- Dr. KAMLA
CHAUDHARY
PRESENTED BY- SHALINI
SAINI
M.Sc- 3RD
SEM
MOLECULAR
MICROBIOLOGY

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INTRODUCTION
• In eukaryotes, the classical form of programmed cell death
(PCD) is apoptosis, which has as its specific characteristics
DNA
• Fragmentation and membrane depolarization. In
Escherichia coli a different PCD system has been reported.
• It is mediated bythe toxin–antitoxin system module
mazEF. The E. coli mazEF module is one of the most
thoroughly studied toxin–antitoxin systems.
• MazF encodes a stable toxin, MazF, and mazE encodes a
labile antitoxin, MazE, which prevents the lethal effect of
MazF.
• mazEF-mediated cell death is a population phenomenon
requiring the quorum-sensing pentapeptide NNWNN
designated Extracellular Death Factor (EDF).
• mazEF is triggered by several stressful conditions,
including severe damage to the DNA.

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• Under the conditions of severe DNA damage, the
triggered mazEF-mediated cell death pathway leads to
the inhibition of a second cell death pathway.
• The latter is an apoptotic-like death (ALD); ALD is
mediated by recA and lexA. The mazEF-mediated
pathway reduces recA mRNA levels.
• Based on these results, we offer a molecular model for
the maintenance of an altruistic characteristic in cell
populations.
• The ALD pathway is inhibited by the altruistic EDF-
mazEF-mediated death pathway.

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INTRODUCTION

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Apoptosis pathway in E.coli
• MazEF system of E. coli. The mazEF system of E. coli is
one of the best studied. It was first described as a
mechanism responsible for bacterial PCD .
• The mazF gene encodes a stable cytotoxic protein,
and mazE encodes an unstable antidote to MazF protein,
which is quickly degraded by the ATP-dependent ClpAP
serine protease [ Under balanced growth conditions, as
long as MazE and MazF are coexpressed, MazE
neutralizes the toxic effect of MazF i.e. the toxin is
constantly neutralized by the antitoxin. The MazF toxin is
a “long-lived” protein, an endoribonuclease, which
cleaves RNA in ACA sequences .

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• However, under stress conditions (starvation,
effects of antibiotics, reactive oxygen species,
presence of 3,5′-bispyrophosphate (ppGpp),
DNA damage), which prevent expression of
the mazEF operon, the equilibrium is disturbed,
and the toxin “poisons” the cell, destroying the
cellular mRNA, which leads to cell death and
autolysis of the greater part of the population
• Under stressful conditions, the labile protein
antitoxin MazE is destroyed by the ClpAP
protease, and as a result the more stable MazF
toxin is free to act, ultimately causing cell death.

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• Extensive DNA damage can lead to cell death following a
second pathway called apoptotic-like death (ALD)
• . ALD is similar to apoptosis of eukaryotic cells. The cell
membrane is depolarized and DNA is fragmented in the
course of this process. ALD to result from the activity of
two proteins, RecA and LexA.
• . LexA protein is an inhibitor of the SOS response, which
is a global response of a bacterial cell to DNA damage,
when the cell cycle is interrupted and DNA reparation is
induced. Thus, ALD can be defined as a form of SOS
response.
• In E. coli cells, the ALD pathway is a backup system in
relation to mazEF, the main pathway of cell death . If
some components of the mazEF pathway are inactivated,
bacterial cell death will follow the ALD pathway
• . In this case RecA inactivates LexA, which is a repressor
of the transcription of SOS-system genes. Essentially, the
destruction of LexA protein activates the SOS response.
The mazEF system-mediated mechanism of cell death
also inhibits the ALD pathway by reducing the mRNA
level of RecA protein.

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CENTRAL REGULATOR

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THE FUNCTION OF ROS AND YihE
• The YihE protein kinase is a key regulator that protects
Escherichia coli from antimicrobial and environmental
stressors by antagonizing the MazEF toxin-antitoxin
module.
• YihE was linked to a reactive oxygen species (ROS)
cascade, and a deficiency of yihE stimulated stress-
induced PCD even after stress dissipated.
• YihE was partially regulated by the Cpx envelope stress-
response system, which, along with MazF toxin and
superoxide, has both protective and destructive roles that
help bacteria make a live-or-die decision in response to
stress.
• YihE probably acts early in the stress response to limit
self-sustaining ROS production and PCD. Inhibition of
YihE may provide a way of enhancing antimicrobial
lethality and attenuating virulence.

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The enteric bacterium E.coli 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, the 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 PCD PATHWAY IN E.coli

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The MazEF death pathway, however, shows neither of those
features, yet also kills the cell.
Here shown 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 .
of the components of the mazEF pathway be inactivated,
bacterial cell death would occur through ALD.

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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.

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COMMON FUNCTION IN ALL BACTERIAL CELL

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The genes switched on and off during
apoptosis

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References
• Microbiology and molecular biology riveiws10.1128/MMBR.64.3.503-
514.2000. Microbiol. Mol. Biol. Rev. 2000, 64(3):503. DOI: Kim Lewis
Programmed Death in Bacteria.
Two Programmed Cell Death Systems in Escherichia coli: An Apoptotic-Like
Death Is Inhibited by the mazEFMediated Death Pathway Ariel Erental, Idith
Sharon, Hanna Engelberg-Kulka* Department of Microbiology and
Molecular Genetics, Institute for Medical Research Israel-Canada, The
Hebrew University-Hadassah Medical School, Jerusalem, Israel
• Molecular Microbiology (2006) First published online 7 November 2005
• Journal compilation © 2005 Blackwell Publishing Ltd
• Blackwell Science, LtdOxford, UKMMIMolecular Microbiology0950-382X©
2005 The Authors; Journal compilation © 2005 Blackwell Publishing Ltd
• Original Article
• MazG – PCD regulator in E. coliM. Gross, I. Marianovsky and G.
• Glaser
• MazG – a regulator of programmed cell death in Escherichia coli Miryam
Gross, Irina Marianovsky and Gad Glaser* Department of Cellular
Biochemistry and Human Genetics, The Hebrew University –Hadassah
Medical School, Jerusalem, Israel.

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