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Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

Erental A, Sharon I, Engelberg-Kulka H - PLoS Biol. (2012)

Bottom Line: 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.In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.

ABSTRACT
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 by the 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. Here, using confocal microscopy and FACS analysis, we show that under 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. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

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A suggested model for the inhibition of the recA- and lexA-mediated apoptotic-like pathway by the EDF-mazEF pathway.Our model is based on the mazEF downstream pathway [27] and the EDF-mazEF-mediated cell death pathway [16],[24]–[28] that we have described previously [16],[24]–[28] and on the recA- and lexA-mediated apoptotic-like pathway on which we have reported here. For additional explanations see also Results and Discussion.
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pbio-1001281-g007: A suggested model for the inhibition of the recA- and lexA-mediated apoptotic-like pathway by the EDF-mazEF pathway.Our model is based on the mazEF downstream pathway [27] and the EDF-mazEF-mediated cell death pathway [16],[24]–[28] that we have described previously [16],[24]–[28] and on the recA- and lexA-mediated apoptotic-like pathway on which we have reported here. For additional explanations see also Results and Discussion.

Mentions: Every living organism must face the challenge of surviving stressful conditions. We assume that in bacteria this function may also be served by genetically programmed cell death pathways. As in case of the EDF-mazEF pathway, the ALD death pathway permits cell survival; a small fraction (below 10%) of the cultures still survived after the deletion of either mazEF or recA (Figure S8). Nevertheless, we suggest that the mechanisms permitting cell survival in the mazEF and ALD pathways are operating at two different levels. As described above, the altruistic mazEF pathway operates on the level of the bacterial population. Survival of a small subpopulation is due to an altruistic death of most of the population, and is therefore “population dependent” (Figure 7). We suggest that, in contrast, the ALD pathway operates on the level of the individual cell, and therefore it is by definition not altruistic. Survival seems to be due to the repair of individual damaged cells (Figure 7). Moreover, while EDF-mazEF is triggered by many kinds of stressful conditions [14],[16],[24],[25],[28], we found here that the ALD pathway is triggered only by DNA damage (Figures 1 and S1). Further studies are needed to examine whether the mazEF pathway is indeed a survival solution on the population level while ALD acts only on the level of the individual cell. ALD appears to be similar to eukaryotic apoptosis, because unlike the EDF-mazEF pathway, the recA-dependent death pathway involves both membrane depolarization and DNA fragmentation (Figures 1 and 3). Further studies will be necessary to clarify whether ALD may share additional characteristics with eukaryotic apoptotic pathways. If so, it may be possible to find some evolutionary connections between eukaryotic apoptotic pathways and the prokaryotic ALD. Recent publications [45]–[48] provide evidence that in eukaryotes, the two PCD pathways, apoptosis and necrosis, are intertwined. More specifically, proteins participating in the apoptotic pathway act together to suppress another type of PCD, necrosis. Clearly, these eukaryotic death pathways are more closely intertwined than was previously thought. Here, to our knowledge for the first time, we show that a similar phenomenon also takes place in prokaryotes, where PCD is not an obvious event, suggesting that the intertwining of PCD systems may be a general biological phenomenon.


Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

Erental A, Sharon I, Engelberg-Kulka H - PLoS Biol. (2012)

A suggested model for the inhibition of the recA- and lexA-mediated apoptotic-like pathway by the EDF-mazEF pathway.Our model is based on the mazEF downstream pathway [27] and the EDF-mazEF-mediated cell death pathway [16],[24]–[28] that we have described previously [16],[24]–[28] and on the recA- and lexA-mediated apoptotic-like pathway on which we have reported here. For additional explanations see also Results and Discussion.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3295820&req=5

pbio-1001281-g007: A suggested model for the inhibition of the recA- and lexA-mediated apoptotic-like pathway by the EDF-mazEF pathway.Our model is based on the mazEF downstream pathway [27] and the EDF-mazEF-mediated cell death pathway [16],[24]–[28] that we have described previously [16],[24]–[28] and on the recA- and lexA-mediated apoptotic-like pathway on which we have reported here. For additional explanations see also Results and Discussion.
Mentions: Every living organism must face the challenge of surviving stressful conditions. We assume that in bacteria this function may also be served by genetically programmed cell death pathways. As in case of the EDF-mazEF pathway, the ALD death pathway permits cell survival; a small fraction (below 10%) of the cultures still survived after the deletion of either mazEF or recA (Figure S8). Nevertheless, we suggest that the mechanisms permitting cell survival in the mazEF and ALD pathways are operating at two different levels. As described above, the altruistic mazEF pathway operates on the level of the bacterial population. Survival of a small subpopulation is due to an altruistic death of most of the population, and is therefore “population dependent” (Figure 7). We suggest that, in contrast, the ALD pathway operates on the level of the individual cell, and therefore it is by definition not altruistic. Survival seems to be due to the repair of individual damaged cells (Figure 7). Moreover, while EDF-mazEF is triggered by many kinds of stressful conditions [14],[16],[24],[25],[28], we found here that the ALD pathway is triggered only by DNA damage (Figures 1 and S1). Further studies are needed to examine whether the mazEF pathway is indeed a survival solution on the population level while ALD acts only on the level of the individual cell. ALD appears to be similar to eukaryotic apoptosis, because unlike the EDF-mazEF pathway, the recA-dependent death pathway involves both membrane depolarization and DNA fragmentation (Figures 1 and 3). Further studies will be necessary to clarify whether ALD may share additional characteristics with eukaryotic apoptotic pathways. If so, it may be possible to find some evolutionary connections between eukaryotic apoptotic pathways and the prokaryotic ALD. Recent publications [45]–[48] provide evidence that in eukaryotes, the two PCD pathways, apoptosis and necrosis, are intertwined. More specifically, proteins participating in the apoptotic pathway act together to suppress another type of PCD, necrosis. Clearly, these eukaryotic death pathways are more closely intertwined than was previously thought. Here, to our knowledge for the first time, we show that a similar phenomenon also takes place in prokaryotes, where PCD is not an obvious event, suggesting that the intertwining of PCD systems may be a general biological phenomenon.

Bottom Line: 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.In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.

ABSTRACT
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 by the 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. Here, using confocal microscopy and FACS analysis, we show that under 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. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

Show MeSH
Related in: MedlinePlus