Two genes, pemK and pemI, responsible for stable maintenance of resistance plasmid R100

Tsuchimoto, Suguru; Ohtsubo, Hisao; Ohtsubo, Eiichi

doi:10.1128/jb.170.4.1461-1466.1988

Cited by 139 publications

(104 citation statements)

References 27 publications

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“…The plasmid maintenance function of TA systems has been well established 1,2 , but increasing number of recent studies suggest a regulatory role of TA systems in broadly defined stress response 7,31 . Our current understanding of the latter function of TA systems is largely speculative, but if confirmed, TA systems are likely to emerge as one of the most versatile global regulatory systems in bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…T oxin-antitoxin (TA) systems were initially characterized as components of low copy number plasmids, which ensured their stable maintenance 1,2 . It was established that daughter cells that lose the plasmid are selectively eliminated by the deleterious activity of the long half-life toxin, as the pool of labile antitoxin rapidly diminishes in the absence of synthesis of new molecules.…”

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confidence: 99%

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A regulatory role for Staphylococcus aureus toxin–antitoxin system PemIKSa

et al. 2013

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Toxin-antitoxin systems were shown to be involved in plasmid maintenance when they were initially discovered, but other roles have been demonstrated since. Here we identify and characterize a novel toxin-antitoxin system (pemIK Sa ) located on Staphylococcus aureus plasmid pCH91. The toxin (PemK Sa ) is a sequence-specific endoribonuclease recognizing the tetrad sequence UkAUU, and the antitoxin (PemI Sa ) inhibits toxin activity by physical interaction. Although the toxin-antitoxin system is responsible for stable plasmid maintenance our data suggest the participation of pemIK Sa in global regulation of staphylococcal virulence by alteration of the translation of large pools of genes. We propose a common mechanism of reversible activation of toxin-antitoxin systems based on antitoxin transcript resistance to toxin cleavage. Elucidation of this mechanism is particularly interesting because reversible activation is a prerequisite for the proposed general regulatory role of toxin-antitoxin systems.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

A regulatory role for Staphylococcus aureus toxin–antitoxin system PemIKSa

et al. 2013

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“…The toxin Kid (PemK) and antitoxin Kis (PemI) are encoded by the parD operon of plasmid R1, 9 which is identical with pem on plasmid R100. 10 Kid inhibits cell growth in E. coli and Kis counteracts this effect. 11 The coordinate action of Kid and Kis has been shown to autoregulate parD at the level of transcription.…”

Section: Introductionmentioning

confidence: 99%

Model for RNA Binding and the Catalytic Site of the RNase Kid of the Bacterial parD Toxin–Antitoxin System

Kamphuis

Bonvin

Monti

et al. 2006

Journal of Molecular Biology

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The toxin Kid and antitoxin Kis are encoded by the parD operon of Escherichia coli plasmid R1. Kid and its chromosomal homologues MazF and ChpBK have been shown to inhibit protein synthesis in cell extracts and to act as ribosome-independent endoribonucleases in vitro. Kid cleaves RNA preferentially at the 5 0 side of the A residue in the nucleotide sequence 5 0 -UA(A/C)-3 0 of single-stranded regions. Here, we show that RNA cleavage by Kid yields two fragments with a 2 0 :3 0 -cyclic phosphate group and a free 5 0 -OH group, respectively. The cleavage mechanism is similar to that of RNases A and T1, involving the uracil 2 0 -OH group. Via NMR titration studies with an uncleavable RNA mimic, we demonstrate that residues of both monomers of the Kid dimer together form a concatenated RNA-binding surface. Docking calculations based on the NMR chemical shifts, the cleavage mechanism and previously reported mutagenesis data provide a detailed picture of the position of the AUACA fragment within the binding pocket. We propose that residues D75, R73 and H17 form the active site of the Kid toxin, where D75 and R73 are the catalytic base and acid, respectively. The RNA sequence specificity is defined by residues T46, S47, A55, F57, T69, V71 and R73. Our data show the importance of these residues for Kid function, and the implications of our results for related toxins, such as MazF, CcdB and RelE, are discussed.

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“…The pemI-pemK system and the kis-kid system are involved in the stable maintenance of two closely related incFII low copy plasmids, plasmid R100 (14,15) and plasmid R1 (10,32), respectively. These two systems turned out to be identical (1).…”

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confidence: 99%

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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Two genes, pemK and pemI, responsible for stable maintenance of resistance plasmid R100

Cited by 139 publications

References 27 publications

A regulatory role for Staphylococcus aureus toxin–antitoxin system PemIKSa

A regulatory role for Staphylococcus aureus toxin–antitoxin system PemIKSa

Model for RNA Binding and the Catalytic Site of the RNase Kid of the Bacterial parD Toxin–Antitoxin System

Interference of mRNA Function by Sequence-specific Endoribonuclease PemK

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