An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death.

Aizenman, Einat; Engelberg‐Kulka, Hanna; Glaser, Gad

doi:10.1073/pnas.93.12.6059

Cited by 561 publications

(705 citation statements)

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“…The most studied extrachromosomal addiction modules are the phd-doc system on bacteriophage P1 (2)(3)(4)(5), the ccdA-ccdB system on factor F (6 -9), the kis-kid system on plasmid R1 (10 -13), and the pemIpemK system on plasmid R100 (14 -17). Interestingly, the E. coli chromosome also contains several addiction module systems, such as the relBE system (18 -21), the mazEF system (22)(23)(24)(25), and the chpB system (26 -28).…”

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Interference of mRNA Function by Sequence-specific Endoribonuclease PemK

Zhang

Zhu

et al. 2004

Journal of Biological Chemistry

122

149

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In Escherichia coli, programmed cell death is mediated through the system called "addiction module," which consists of a pair of genes encoding a stable toxin and a labile antitoxin. The pemI-pemK system is an addiction module present on plasmid R100. It helps to maintain the plasmid by post-segregational killing in E. coli population. Here we demonstrate that purified PemK, the toxin encoded by the pemI-pemK addiction module, inhibits protein synthesis in an E. coli cell-free system, whereas the addition of PemI, the antitoxin against PemK, resumes the protein synthesis. Further studies reveal that PemK is a sequence-specific endoribonuclease that cleaves mRNAs to inhibit protein synthesis, whereas PemI blocks the endoribonuclease activity of PemK. PemK cleaves only single-stranded RNA preferentially at the 5 or 3 side of the A residue in the "UAH" sequences (where H is C, A, or U). Upon induction, PemK cleaves cellular mRNAs to effectively block protein synthesis in E. coli. The pemK homologue genes have been identified on the genomes of a wide range of bacteria. We propose that PemK and its homologues form a novel endoribonuclease family that interferes with mRNA function by cleaving cellular mRNAs in a sequence-specific manner.In Escherichia coli, programmed cell death is proposed to be mediated through the system called "addiction module," which consists of a pair of genes encoding a toxin and an antitoxin (1). The addiction module has the following properties. (a) The toxic protein is stable, whereas the antitoxin is a labile protein. (b) The toxin and the antitoxin are coexpressed from an operon and interact with each other to form a stable complex. (c) Their expression is auto-regulated either by the toxin-antitoxin complex or by the antitoxin alone. When the co-expression is inhibited under stress conditions, the antitoxin is degraded by proteases, enabling the toxin to act on its target. In E. coli, some extrachromosomal elements are known to contain addiction modules causing the bacterial programmed cell death by the so-called postsegregational killing effect. The most studied extrachromosomal addiction modules are the phd-doc system on bacteriophage P1 (2-5), the ccdA-ccdB system on factor F (6 -9), the kis-kid system on plasmid R1 (10 -13), and the pemIpemK system on plasmid R100 (14 -17). Interestingly, the E. coli chromosome also contains several addiction module systems, such as the relBE system (18 -21), the mazEF system (22-25), and the chpB system (26 -28).The cellular effects of the toxins in the addiction modules have been studied quite extensively. CcdB, the toxin in the ccdA-ccdB system, interacts with DNA gyrase to block DNA replication (7,29), and RelE, the toxin in the relBE system, is not able to degrade free RNA but cleaves mRNA in the ribosome A site with high codon specificity (21). Recently, it was demonstrated that the A-site mRNA cleavage can occur in the absence of RelE (30). The exact mechanism of the A-site mRNA cleavage is still unknown. It has been proposed that MazF (ChpAK)...

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Interference of mRNA Function by Sequence-specific Endoribonuclease PemK

Zhang

Zhu

et al. 2004

Journal of Biological Chemistry

122

149

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“…For example, in E. coli, there are several such pairs of genes, including mazEF (23)(24)(25), chpBIK (24), relBE (26 -28), yefM-yoeB (29 -31), and dinJ-yafQ (32). The first toxin-antitoxin system contained in a bacterial chromosome that was described as regulatable and responsible for programmed cell death was the E. coli mazEF module (25), located in the relA operon (23). The product of mazF (MazF) is a stable toxin, and the product of mazE (MazE) is a labile protein, degraded by the protease ClpAP (25).…”

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confidence: 99%

“…In contrast to the addiction modules that are triggered by the loss of the element, death mediated by chromosomal mazEF is achieved by several stressful conditions that prevent mazEF expression. Initially, the mazEF module was found to be under the control of ppGpp (25), the amino acid starvation signal molecule produced by the RelA protein (33). Overproduction of ppGpp leads to inhibition of the expression of mazEF and thereby to cell death (25,34).…”

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confidence: 99%

“…Initially, the mazEF module was found to be under the control of ppGpp (25), the amino acid starvation signal molecule produced by the RelA protein (33). Overproduction of ppGpp leads to inhibition of the expression of mazEF and thereby to cell death (25,34). However, as reported recently, inhibiting the expression of mazEF and thus inducing cell death can be also achieved by several additional stressful conditions.…”

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confidence: 99%

“…The first toxin-antitoxin system contained in a bacterial chromosome that was described as regulatable and responsible for programmed cell death was the E. coli mazEF module (25), located in the relA operon (23). The product of mazF (MazF) is a stable toxin, and the product of mazE (MazE) is a labile protein, degraded by the protease ClpAP (25). Therefore, preventing MazF-mediated death requires a continuous cellular production of MazE.…”

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confidence: 99%

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Energetics of Structural Transitions of the Addiction Antitoxin MazE

Lah

Simic

Vesnaver

et al. 2005

Journal of Biological Chemistry

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The Escherichia coli mazEF addiction module plays a crucial role in the cell death program that is triggered under various stress conditions. It codes for the toxin MazF and the antitoxin MazE, which interferes with the lethal action of the toxin. To better understand the role of various conformations of MazE in bacterial life, its order-disorder transitions were monitored by differential scanning calorimetry, spectropolarimetry, and fluorimetry. The changes in spectral and thermodynamic properties accompanying MazE dimer denaturation can be described in terms of a compensating reversible process of the partial folding of the unstructured C-terminal half (high mean net charge, low mean hydrophobicity) and monomerization coupled with the partial unfolding of the structured N-terminal half (low mean net charge, high mean hydrophobicity). At pH < 4.5 and T < 50°C, the unstructured polypeptide chains of the MazE dimer fold into (pre)molten globule-like conformations that thermally stabilize the dimeric form of the protein. The simulation based on the thermodynamic and structural information on various addiction modules suggests that both the conformational adaptability of the dimeric antitoxin form (binding to the toxins and DNA) and the reversible transformation to the more flexible monomeric form are essential for the regulation of bacterial cell life and death.

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Viable but not Culturable (VBNC) Microorganisms

Koch

2003

Encyclopedia of Environmental Microbiology

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The Concept of the Viable but non Culturable (VBNC) Cell The Reality of the VBNC Phenomenon Other Cases of Organisms ‘Choosing’ not to Grow Maximally Still Other Kinds of Lethal Processes The Different kinds of Bacterial Death

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An Escherichia coli chromosomal "addiction module" regulated by guanosine [corrected] 3',5'-bispyrophosphate: a model for programmed bacterial cell death.

Cited by 561 publications

References 35 publications

Interference of mRNA Function by Sequence-specific Endoribonuclease PemK

Interference of mRNA Function by Sequence-specific Endoribonuclease PemK

Energetics of Structural Transitions of the Addiction Antitoxin MazE

Viable but not Culturable (VBNC) Microorganisms

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