Toxins-antitoxins: diversity, evolution and function

References

• Afif H, Allali N, Couturier M, Van Melderen L. 2001. The ratio between CcdA and CcdB modulates the transcriptional repression of the ccd poison-antidote system. Mol Microbiol 41:73–82.
   Google Scholar
• Agarwal S, Mishra NK, Bhatnagar S, Bhatnagar R. 2010. PemK toxin of Bacillus anthracis is a ribonuclease: An insight into its active site, structure, and function. J Biol Chem 285:7254–7270.
   Google Scholar
• Aizenman E, Engelberg-Kulka H, Glaser G. 1996. An Escherichia coli chromosomal “addiction module” regulated by guanosine [corrected] 3′,5′-bispyrophosphate: A model for programmed bacterial cell death. Proc Natl Acad Sci USA 93:6059–6063.
   PubMed Web of Science ®Google Scholar
• Amitai S, Kolodkin-Gal I, Hananya-Meltabashi M, Sacher A, Engelberg-Kulka H. 2009. Escherichia coli MazF leads to the simultaneous selective synthesis of both “death proteins” and “survival proteins”. PLoS Genet 5:e1000390.
   Google Scholar
• Amitai S, Yassin Y, Engelberg-Kulka H. 2004. MazF-mediated cell death in Escherichia coli: A point of no return. J Bacteriol 186:8295–8300.
   Google Scholar
• Anantharaman V, Aravind L. 2003. New connections in the prokaryotic toxin-antitoxin network: Relationship with the eukaryotic nonsense-mediated RNA decay system. Genome Biol 4:R81.
   Web of Science ®Google Scholar
• Andreev D, Hauryliuk V, Terenin I, Dmitriev S, Ehrenberg M, Shatsky I. 2008. The bacterial toxin RelE induces specific mRNA cleavage in the A site of the eukaryote ribosome. RNA 14:233–239.
   PubMed Web of Science ®Google Scholar
• Arbing MA, Handelman SK, Kuzin AP, Verdon G, Wang C, Su M, Rothenbacher FP, Abashidze M, Liu M, Hurley JM, Xiao R, Acton T, Inouye M, Montelione GT, Woychik NA, Hunt JF. 2010. Crystal structures of Phd-Doc, HigA, and YeeU establish multiple evolutionary links between microbial growth-regulating toxin-antitoxin systems. Structure 18:996–1010.
   Google Scholar
• Arcus VL, Bäckbro K, Roos A, Daniel EL, Baker EN. 2004. Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease. J Biol Chem 279:16471–16478.
   PubMedGoogle Scholar
• Arcus VL, McKenzie JL, Robson J, Cook GM. 2011. The PIN-domain ribonucleases and the prokaryotic VapBC toxin-antitoxin array. Protein Eng Des Sel 24:33–40.
   PubMed Web of Science ®Google Scholar
• Bahassi EM, O’Dea MH, Allali N, Messens J, Gellert M, Couturier M. 1999. Interactions of CcdB with DNA gyrase. Inactivation of GyrA, poisoning of the gyrase-DNA complex, and the antidote action of CcdA. J Biol Chem 274:10936–10944.
   Google Scholar
• Baik S, Inoue K, Ouyang M, Inouye M. 2009. Significant bias against the ACA triplet in the tmRNA sequence of Escherichia coli K-12. J Bacteriol 191:6157–6166.
   Google Scholar
• Bailey SE, Hayes F. 2009. Influence of operator site geometry on transcriptional control by the YefM-YoeB toxin-antitoxin complex. J Bacteriol 191:762–772.
   Google Scholar
• Barbosa LC, Garrido SS, Garcia A, Delfino DB, Marchetto R. 2010. Function inferences from a molecular structural model of bacterial ParE toxin. Bioinformation 4:438–440.
   Google Scholar
• Belitsky M, Avshalom H, Erental A, Yelin I, Kumar S, London N, Sperber M, Schueler-Furman O, Engelberg-Kulka H. 2011. The Escherichia coli extracellular death factor EDF induces the endoribonucleolytic activities of the toxins MazF and ChpBK. Mol Cell 41:625–635.
   PubMed Web of Science ®Google Scholar
• Bernard P, Couturier M. 1992. Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. J Mol Biol 226:735–745.
   PubMed Web of Science ®Google Scholar
• Bernard P, Gabant P, Bahassi EM, Couturier M. 1994. Positive-selection vectors using the F plasmid ccdB killer gene. Gene 148:71–74.
   PubMed Web of Science ®Google Scholar
• Bex F, Karoui H, Rokeach L, Drèze P, Garcia L, Couturier M. 1983. Mini-F encoded proteins: Identification of a new 10.5 kilodalton species. EMBO J 2:1853–1861.
   Google Scholar
• Blower TR, Fineran PC, Johnson MJ, Toth IK, Humphreys DP, Salmond GP. 2009. Mutagenesis and functional characterization of the RNA and protein components of the toxIN abortive infection and toxin-antitoxin locus of Erwinia. J Bacteriol 191:6029–6039.
   PubMedGoogle Scholar
• Blower TR, Pei XY, Short FL, Fineran PC, Humphreys DP, Luisi BF, Salmond GP. 2011a. A processed noncoding RNA regulates an altruistic bacterial antiviral system. Nat Struct Mol Biol 18:185–190.
   PubMed Web of Science ®Google Scholar
• Blower TR, Salmond GP, Luisi BF. 2011b. Balancing at survival′s edge: The structure and adaptive benefits of prokaryotic toxin-antitoxin partners. Curr Opin Struct Biol 21:109–118.
   PubMed Web of Science ®Google Scholar
• Bobay BG, Andreeva A, Mueller GA, Cavanagh J, Murzin AG. 2005. Revised structure of the AbrB N-terminal domain unifies a diverse superfamily of putative DNA-binding proteins. FEBS Lett 579:5669–5674.
   Google Scholar
• Bravo A, de Torrontegui G, Díaz R. 1987. Identification of components of a new stability system of plasmid R1, ParD, that is close to the origin of replication of this plasmid. Mol Gen Genet 210:101–110.
   Google Scholar
• Brown BL, Grigoriu S, Kim Y, Arruda JM, Davenport A, Wood TK, Peti W, Page R. 2009. Three dimensional structure of the MqsR:MqsA complex: A novel TA pair comprised of a toxin homologous to RelE and an antitoxin with unique properties. PLoS Pathog 5:e1000706.
   Google Scholar
• Brown BL, Wood TK, Peti W, Page R. 2011. Structure of the Escherichia coli antitoxin MqsA (YgiT/b3021) bound to its gene promoter reveals extensive domain rearrangements and the specificity of transcriptional regulation. J Biol Chem 286:2285–2296.
   Google Scholar
• Brown JM, Shaw KJ. 2003. A novel family of Escherichia coli toxin-antitoxin gene pairs. J Bacteriol 185:6600–6608.
   PubMed Web of Science ®Google Scholar
• Budde PP, Davis BM, Yuan J, Waldor MK. 2007. Characterization of a higBA toxin-antitoxin locus in Vibrio cholerae. J Bacteriol 189:491–500.
   PubMed Web of Science ®Google Scholar
• Camacho AG, Misselwitz R, Behlke J, Ayora S, Welfle K, Meinhart A, Lara B, Saenger W, Welfle H, Alonso JC. 2002. In vitro and in vivo stability of the ε2ζ2 protein complex of the broad host-range Streptococcus pyogenes pSM19035 addiction system. Biol Chem 383:1701–1713.
   Google Scholar
• Cambray G, Guerout AM, Mazel D. 2010. Integrons. Annu Rev Genet 44:141–166.
   PubMed Web of Science ®Google Scholar
• Ceglowski P, Boitsov A, Chai S, Alonso JC. 1993. Analysis of the stabilization system of pSM19035-derived plasmid pBT233 in Bacillus subtilis. Gene 136:1–12.
   Google Scholar
• Cherny I, Gazit E. 2004. The YefM antitoxin defines a family of natively unfolded proteins: Implications as a novel antibacterial target. J Biol Chem 279:8252–8261.
   Google Scholar
• Cherny I, Overgaard M, Borch J, Bram Y, Gerdes K, Gazit E. 2007. Structural and thermodynamic characterization of the Escherichia coli RelBE toxin-antitoxin system: Indication for a functional role of differential stability. Biochemistry 46:12152–12163.
   Google Scholar
• Chono H, Matsumoto K, Tsuda H, Saito N, Lee K, Kim S, Shibata H, Ageyama N, Terao K, Yasutomi Y, Mineno J, Kim S, Inouye M, Kato I. 2011. Acquisition of HIV-1 resistance in T lymphocytes using an ACA-specific E. coli mRNA interferase. Hum Gene Ther 22:35–43.
   Google Scholar
• Chopra N, Agarwal S, Verma S, Bhatnagar S, Bhatnagar R. 2011. Modeling of the structure and interactions of the B. anthracis antitoxin, MoxX: Deletion mutant studies highlight its modular structure and repressor function. J Comput Aided Mol Des 25:275–291.
   Google Scholar
• Christensen SK, Gerdes K. 2003. RelE toxins from bacteria and Archaea cleave mRNAs on translating ribosomes, which are rescued by tmRNA. Mol Microbiol 48:1389–1400.
   PubMed Web of Science ®Google Scholar
• Christensen SK, Maenhaut-Michel G, Mine N, Gottesman S, Gerdes K, Van Melderen L. 2004. Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: Involvement of the yefM-yoeB toxin-antitoxin system. Mol Microbiol 51:1705–1717.
   PubMed Web of Science ®Google Scholar
• Christensen SK, Mikkelsen M, Pedersen K, Gerdes K. 2001. RelE, a global inhibitor of translation, is activated during nutritional stress. Proc Natl Acad Sci USA 98:14328–14333.
   PubMed Web of Science ®Google Scholar
• Christensen SK, Pedersen K, Hansen FG, Gerdes K. 2003. Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA. J Mol Biol 332:809–819.
   PubMed Web of Science ®Google Scholar
• Christensen-Dalsgaard M, Gerdes K. 2006. Two higBA loci in the Vibrio cholerae superintegron encode mRNA cleaving enzymes and can stabilize plasmids. Mol Microbiol 62:397–411.
   Google Scholar
• Christensen-Dalsgaard M, Gerdes K. 2008. Translation affects YoeB and MazF messenger RNA interferase activities by different mechanisms. Nucleic Acids Res 36:6472–6481.
   Google Scholar
• Christensen-Dalsgaard M, Jørgensen MG, Gerdes K. 2010. Three new RelE-homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses. Mol Microbiol 75:333–348.
   PubMed Web of Science ®Google Scholar
• Cooper CR, Daugherty AJ, Tachdjian S, Blum PH, Kelly RM. 2009. Role of vapBC toxin-antitoxin loci in the thermal stress response of Sulfolobus solfataricus. Biochem Soc Trans 37:123–126.
   Google Scholar
• Cooper TF, Heinemann JA. 2000. Postsegregational killing does not increase plasmid stability but acts to mediate the exclusion of competing plasmids. Proc Natl Acad Sci USA 97:12643–12648.
   Google Scholar
• Correia FF, D′Onofrio A, Rejtar T, Li L, Karger BL, Makarova K, Koonin EV, Lewis K. 2006. Kinase activity of overexpressed HipA is required for growth arrest and multidrug tolerance in Escherichia coli. J Bacteriol 188:8360–8367.
   PubMed Web of Science ®Google Scholar
• Critchlow SE, O′Dea MH, Howells AJ, Couturier M, Gellert M, Maxwell A. 1997. The interaction of the F plasmid killer protein, CcdB, with DNA gyrase: Induction of DNA cleavage and blocking of transcription. J Mol Biol 273:826–839.
   PubMedGoogle Scholar
• Daines DA, Wu MH, Yuan SY. 2007. VapC-1 of nontypeable Haemophilus influenzae is a ribonuclease. J Bacteriol 189:5041–5048.
   Google Scholar
• Dalton KM, Crosson S. 2010. A conserved mode of protein recognition and binding in a ParD-ParE toxin-antitoxin complex. Biochemistry 49:2205–2215.
   Google Scholar
• Dao-Thi MH, Charlier D, Loris R, Maes D, Messens J, Wyns L, Backmann J. 2002. Intricate interactions within the ccd plasmid addiction system. J Biol Chem 277:3733–3742.
   Google Scholar
• Dao-Thi MH, Van Melderen L, De Genst E, Afif H, Buts L, Wyns L, Loris R. 2005. Molecular basis of gyrase poisoning by the addiction toxin CcdB. J Mol Biol 348:1091–1102.
   PubMed Web of Science ®Google Scholar
• De Jonge N, Garcia-Pino A, Buts L, Haesaerts S, Charlier D, Zangger K, Wyns L, De Greve H, Loris R. 2009. Rejuvenation of CcdB-poisoned gyrase by an intrinsically disordered protein domain. Mol Cell 35:154–163.
   Google Scholar
• de la Cueva-Méndez G, Mills AD, Clay-Farrace L, Díaz-Orejas R, Laskey RA. 2003. Regulatable killing of eukaryotic cells by the prokaryotic proteins Kid and Kis. EMBO J 22:246–251.
   Google Scholar
• de la Hoz AB, Ayora S, Sitkiewicz I, Fernández S, Pankiewicz R, Alonso JC, Ceglowski P. 2000. Plasmid copy-number control and better-than-random segregation genes of pSM19035 share a common regulator. Proc Natl Acad Sci USA 97:728–733.
   PubMedGoogle Scholar
• Diago-Navarro E, Mora L, Buckingham RH, Díaz-Orejas R, Lemonnier M. 2009. Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE. Mol Microbiol 71:66–78.
   PubMedGoogle Scholar
• Donegan NP, Cheung AL. 2009. Regulation of the mazEF toxin-antitoxin module in Staphylococcus aureus and its impact on sigB expression. J Bacteriol 191:2795–2805.
   PubMed Web of Science ®Google Scholar
• Dörr T, Vulic M, Lewis K. 2010. Ciprofloxacin causes persister formation by inducing the TisB toxin in Escherichia coli. PLoS Biol 8:e1000317.
   PubMed Web of Science ®Google Scholar
• Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R. 2006. Bacterial programmed cell death and multicellular behavior in bacteria. PLoS Genet 2:e135.
   PubMed Web of Science ®Google Scholar
• Engelberg-Kulka H, Glaser G. 1999. Addiction modules and programmed cell death and antideath in bacterial cultures. Annu Rev Microbiol 53:43–70.
   PubMed Web of Science ®Google Scholar
• Engelberg-Kulka H, Sat B, Reches M, Amitai S, Hazan R. 2004. Bacterial programmed cell death systems as targets for antibiotics. Trends Microbiol 12:66–71.
   Google Scholar
• Engelberg-Kulka H, Yelin I, Kolodkin-Gal I. 2009. Activation of a built-in bacterial programmed cell death system as a novel mechanism of action of some antibiotics. Commun Integr Biol 2:211–212.
   PubMedGoogle Scholar
• Erickson HP, Anderson DE, Osawa M. 2010. FtsZ in bacterial cytokinesis: Cytoskeleton and force generator all in one. Microbiol Mol Biol Rev 74:504–528.
   PubMedGoogle Scholar
• Fey PD. 2010. Modality of bacterial growth presents unique targets: How do we treat biofilm-mediated infections? Curr Opin Microbiol 13:610–615.
   PubMed Web of Science ®Google Scholar
• Fiebig A, Castro Rojas CM, Siegal-Gaskins D, Crosson S. 2010. Interaction specificity, toxicity and regulation of a paralogous set of ParE/RelE-family toxin-antitoxin systems. Mol Microbiol 77:236–251.
   Google Scholar
• Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS, Salmond GP. 2009. The phage abortive infection system, ToxIN, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci USA 106:894–899.
   PubMed Web of Science ®Google Scholar
• Fozo EM, Hemm MR, Storz G. 2008. Small toxic proteins and the antisense RNAs that repress them. Microbiol Mol Biol Rev 72:579–589.
   Google Scholar
• Fozo EM, Makarova KS, Shabalina SA, Yutin N, Koonin EV, Storz G. 2010. Abundance of type I toxin-antitoxin systems in bacteria: Searches for new candidates and discovery of novel families. Nucleic Acids Res 38:3743–3759.
   Google Scholar
• Francuski D, Saenger W. 2009. Crystal structure of the antitoxin-toxin protein complex RelB-RelE from Methanococcus jannaschii. J Mol Biol 393:898–908.
   Google Scholar
• Fu Z, Donegan NP, Memmi G, Cheung AL. 2007. Characterization of MazFSa, an endoribonuclease from Staphylococcus aureus. J Bacteriol 189:8871–8879.
   Google Scholar
• Fu Z, Tamber S, Memmi G, Donegan NP, Cheung AL. 2009. Overexpression of MazFsa in Staphylococcus aureus induces bacteriostasis by selectively targeting mRNAs for cleavage. J Bacteriol 191:2051–2059.
   Google Scholar
• Galvani C, Terry J, Ishiguro EE. 2001. Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes. J Bacteriol 183:2700–2703.
   Google Scholar
• García-Contreras R, Zhang XS, Kim Y, Wood TK. 2008. Protein translation and cell death: The role of rare tRNAs in biofilm formation and in activating dormant phage killer genes. PLoS ONE 3:e2394.
   PubMed Web of Science ®Google Scholar
• Garcia-Pino A, Balasubramanian S, Wyns L, Gazit E, De Greve H, Magnuson RD, Charlier D, van Nuland NA, Loris R. 2010. Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativity. Cell 142:101–111.
   Web of Science ®Google Scholar
• Garcia-Pino A, Christensen-Dalsgaard M, Wyns L, Yarmolinsky M, Magnuson RD, Gerdes K, Loris R. 2008. Doc of prophage P1 is inhibited by its antitoxin partner Phd through fold complementation. J Biol Chem 283:30821–30827.
   Google Scholar
• Georgiades K, Raoult D. 2011. Genomes of the most dangerous epidemic bacteria have a virulence repertoire characterized by fewer genes but more toxin-antitoxin modules. PLoS ONE 6:e17962.
   PubMedGoogle Scholar
• Gerdes K. 2000. Toxin-antitoxin modules may regulate synthesis of macromolecules during nutritional stress. J Bacteriol 182:561–572.
   PubMed Web of Science ®Google Scholar
• Gerdes K, Christensen SK, Løbner-Olesen A. 2005. Prokaryotic toxin-antitoxin stress response loci. Nat Rev Microbiol 3:371–382.
   PubMed Web of Science ®Google Scholar
• Gerdes K, Helin K, Christensen OW, Løbner-Olesen A. 1988. Translational control and differential RNA decay are key elements regulating postsegregational expression of the killer protein encoded by the parB locus of plasmid R1. J Mol Biol 203:119–129.
   PubMed Web of Science ®Google Scholar
• Gerdes K, Nielsen A, Thorsted P, Wagner EG. 1992. Mechanism of killer gene activation. Antisense RNA-dependent RNase III cleavage ensures rapid turn-over of the stable hok, srnB and pndA effector messenger RNAs. J Mol Biol 226:637–649.
   Google Scholar
• Gerdes K, Poulsen LK, Thisted T, Nielsen AK, Martinussen J, Andreasen PH. 1990. The hok killer gene family in gram-negative bacteria. New Biol 2:946–956.
   Google Scholar
• Gerdes K, Rasmussen PB, Molin S. 1986. Unique type of plasmid maintenance function: Postsegregational killing of plasmid-free cells. Proc Natl Acad Sci USA 83:3116–3120.
   PubMed Web of Science ®Google Scholar
• Godoy VG, Jarosz DF, Walker FL, Simmons LA, Walker GC. 2006. Y-family DNA polymerases respond to DNA damage-independent inhibition of replication fork progression. EMBO J 25:868–879.
   Google Scholar
• González Barrios AF, Zuo R, Hashimoto Y, Yang L, Bentley WE, Wood TK. 2006. Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (MqsR, B3022). J Bacteriol 188:305–316.
   PubMed Web of Science ®Google Scholar
• Gotfredsen M, Gerdes K. 1998. The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family. Mol Microbiol 29:1065–1076.
   PubMedGoogle Scholar
• Goulard C, Langrand S, Carniel E, Chauvaux S. 2010. The Yersinia pestis chromosome encodes active addiction toxins. J Bacteriol 192:3669–3677.
   Google Scholar
• Grady R, Hayes F. 2003. Axe-Txe, a broad-spectrum proteic toxin-antitoxin system specified by a multidrug-resistant, clinical isolate of Enterococcus faecium. Mol Microbiol 47:1419–1432.
   PubMedGoogle Scholar
• Gross M, Marianovsky I, Glaser G. 2006. MazG−a regulator of programmed cell death in Escherichia coli. Mol Microbiol 59:590–601.
   PubMedGoogle Scholar
• Guglielmini J, Szpirer C, Milinkovitch MC. 2008. Automated discovery and phylogenetic analysis of new toxin-antitoxin systems. BMC Microbiol 8:104.
   Google Scholar
• Hallez R, Geeraerts D, Sterckx Y, Mine N, Loris R, Van Melderen L. 2010. New toxins homologous to ParE belonging to three-component toxin-antitoxin systems in Escherichia coli O157:H7. Mol Microbiol 76:719–732.
   Google Scholar
• Han JS, Lee JJ, Anandan T, Zeng M, Sripathi S, Jahng WJ, Lee SH, Suh JW, Kang CM. 2010. Characterization of a chromosomal toxin-antitoxin, Rv1102c-Rv1103c system in Mycobacterium tuberculosis. Biochem Biophys Res Commun 400:293–298.
   PubMed Web of Science ®Google Scholar
• Han KD, Matsuura A, Ahn HC, Kwon AR, Min YH, Park HJ, Won HS, Park SJ, Kim DY, Lee BJ. 2011. Functional identification of toxin-antitoxin molecules from Helicobacter pylori 26695 and structural elucidation of the molecular interactions. J Biol Chem 286:4842–4853.
   Google Scholar
• Hargreaves D, Santos-Sierra S, Giraldo R, Sabariegos-Jareño R, de la Cueva-Méndez G, Boelens R, Díaz-Orejas R, Rafferty JB. 2002. Structural and functional analysis of the Kid toxin protein from E. coli plasmid R1. Structure 10:1425–1433.
   Google Scholar
• Hayes F. 1998. A family of stability determinants in pathogenic bacteria. J Bacteriol 180:6415–6418.
   Google Scholar
• Hayes F. 2003. Toxins-antitoxins: Plasmid maintenance, programmed cell death, and cell cycle arrest. Science 301:1496–1499.
   PubMedGoogle Scholar
• Hayes F. 2011. Moving in for the kill: Activation of an endoribonuclease toxin by a quorum-sensing peptide. Mol Cell 41:617–618.
   Google Scholar
• Hazan R, Engelberg-Kulka H. 2004. Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1. Mol Genet Genomics 272:227–234.
   PubMed Web of Science ®Google Scholar
• Hazan R, Sat B, Engelberg-Kulka H. 2004. Escherichia coli mazEF-mediated cell death is triggered by various stressful conditions. J Bacteriol 186:3663–3669.
   PubMed Web of Science ®Google Scholar
• Hazan R, Sat B, Reches M, Engelberg-Kulka H. 2001. Postsegregational killing mediated by the P1 phage “addiction module” phd-doc requires the Escherichia coli programmed cell death system mazEF. J Bacteriol 183:2046–2050.
   PubMed Web of Science ®Google Scholar
• Higgins CF, McLaren RS, Newbury SF. 1988. Repetitive extragenic palindromic sequences, mRNA stability and gene expression: Evolution by gene conversion? A review. Gene 72:3–14.
   PubMed Web of Science ®Google Scholar
• Huang F, He ZG. 2010. Characterization of an interplay between a Mycobacterium tuberculosis MazF homolog, Rv1495 and its sole DNA topoisomerase I. Nucleic Acids Res 38:8219–8230.
   Google Scholar
• Hurley JM, Cruz JW, Ouyang M, Woychik NA. 2011. Bacterial toxin RelE mediates frequent codon-independent mRNA cleavage from the 5′ end of coding regions in vivo. J Biol Chem 286:14770–14778.
   Google Scholar
• Hurley JM, Woychik NA. 2009. Bacterial toxin HigB associates with ribosomes and mediates translation-dependent mRNA cleavage at A-rich sites. J Biol Chem 284:18605–18613.
   PubMed Web of Science ®Google Scholar
• Inouye M. 2006. The discovery of mRNA interferases: Implication in bacterial physiology and application to biotechnology. J Cell Physiol 209:670–676.
   PubMed Web of Science ®Google Scholar
• Jaffé A, Ogura T, Hiraga S. 1985. Effects of the ccd function of the F plasmid on bacterial growth. J Bacteriol 163:841–849.
   PubMed Web of Science ®Google Scholar
• Jiang Y, Pogliano J, Helinski DR, Konieczny I. 2002. ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Mol Microbiol 44:971–979.
   PubMed Web of Science ®Google Scholar
• Johnson EP, Strom AR, Helinski DR. 1996. Plasmid RK2 toxin protein ParE: Purification and interaction with the ParD antitoxin protein. J Bacteriol 178:1420–1429.
   Google Scholar
• Jones BV, Sun F, Marchesi JR. 2010. Comparative metagenomic analysis of plasmid encoded functions in the human gut microbiome. BMC Genomics 11:46.
   Google Scholar
• Jørgensen MG, Pandey DP, Jaskolska M, Gerdes K. 2009. HicA of Escherichia coli defines a novel family of translation-independent mRNA interferases in bacteria and archaea. J Bacteriol 191:1191–1199.
   Google Scholar
• Kamada K, Hanaoka F. 2005. Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin. Mol Cell 19:497–509.
   PubMed Web of Science ®Google Scholar
• Kamada K, Hanaoka F, Burley SK. 2003. Crystal structure of the MazE/MazF complex: Molecular bases of antidote-toxin recognition. Mol Cell 11:875–884.
   Google Scholar
• Karoui H, Bex F, Drèze P, Couturier M. 1983. Ham22, a mini-F mutation which is lethal to host cell and promotes recA-dependent induction of lambdoid prophage. EMBO J 2:1863–1868.
   Google Scholar
• Kawano M, Aravind L, Storz G. 2007. An antisense RNA controls synthesis of an SOS-induced toxin evolved from an antitoxin. Mol Microbiol 64:738–754.
   PubMed Web of Science ®Google Scholar
• Kędzierska B, Lian LY, Hayes F. 2007. Toxin-antitoxin regulation: Bimodal interaction of YefM-YoeB with paired DNA palindromes exerts transcriptional autorepression. Nucleic Acids Res 35:325–339.
   Google Scholar
• Keren I, Shah D, Spoering A, Kaldalu N, Lewis K. 2004. Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli. J Bacteriol 186:8172–8180.
   PubMed Web of Science ®Google Scholar
• Khoo SK, Loll B, Chan WT, Shoeman RL, Ngoo L, Yeo CC, Meinhart A. 2007. Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae. J Biol Chem 282:19606–19618.
   Google Scholar
• Kim Y, Wang X, Ma Q, Zhang XS, Wood TK. 2009. Toxin-antitoxin systems in Escherichia coli influence biofilm formation through YjgK (TabA) and fimbriae. J Bacteriol 191:1258–1267.
   PubMed Web of Science ®Google Scholar
• Kim Y, Wang X, Zhang XS, Grigoriu S, Page R, Peti W, Wood TK. 2010. Escherichia coli toxin/antitoxin pair MqsR/MqsA regulate toxin CspD. Environ Microbiol 12:1105–1121.
   PubMed Web of Science ®Google Scholar
• Kolodkin-Gal I, Engelberg-Kulka H. 2006. Induction of Escherichia coli chromosomal mazEF by stressful conditions causes an irreversible loss of viability. J Bacteriol 188:3420–3423.
   PubMed Web of Science ®Google Scholar
• Kolodkin-Gal I, Engelberg-Kulka H. 2008. The extracellular death factor: Physiological and genetic factors influencing its production and response in Escherichia coli. J Bacteriol 190:3169–3175.
   PubMedGoogle Scholar
• Kolodkin-Gal I, Engelberg-Kulka H. 2009. The stationary-phase sigma factor σs is responsible for the resistance of Escherichia coli stationary-phase cells to mazEF-mediated cell death. J Bacteriol 191:3177–3182.
   Google Scholar
• Kolodkin-Gal I, Hazan R, Gaathon A, Carmeli S, Engelberg-Kulka H. 2007. A linear pentapeptide is a quorum-sensing factor required for mazEF-mediated cell death in Escherichia coli. Science 318:652–655.
   PubMed Web of Science ®Google Scholar
• Kolodkin-Gal I, Sat B, Keshet A, Engelberg-Kulka H. 2008. The communication factor EDF and the toxin-antitoxin module mazEF determine the mode of action of antibiotics. PLoS Biol 6:e319.
   Google Scholar
• Kolodkin-Gal I, Verdiger R, Shlosberg-Fedida A, Engelberg-Kulka H. 2009. A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation. PLoS ONE 4:e6785.
   Google Scholar
• Korch SB, Hill TM. 2006. Ectopic overexpression of wild-type and mutant hipA genes in Escherichia coli: Effects on macromolecular synthesis and persister formation. J Bacteriol 188:3826–3836.
   PubMed Web of Science ®Google Scholar
• Kotnik M, Anderluh PS, Prezelj A. 2007. Development of novel inhibitors targeting intracellular steps of peptidoglycan biosynthesis. Curr Pharm Des 13:2283–2309.
   PubMed Web of Science ®Google Scholar
• Krab IM, Parmeggiani A. 2002. Mechanisms of EF-Tu, a pioneer GTPase. Prog Nucleic Acid Res Mol Biol 71:513–551.
   PubMed Web of Science ®Google Scholar
• Kristoffersen P, Jensen GB, Gerdes K, Piskur J. 2000. Bacterial toxin-antitoxin gene system as containment control in yeast cells. Appl Environ Microbiol 66:5524–5526.
   PubMed Web of Science ®Google Scholar
• Kumar P, Issac B, Dodson EJ, Turkenburg JP, Mande SC. 2008. Crystal structure of Mycobacterium tuberculosis YefM antitoxin reveals that it is not an intrinsically unstructured protein. J Mol Biol 383:482–493.
   Google Scholar
• Lehnherr H, Maguin E, Jafri S, Yarmolinsky MB. 1993. Plasmid addiction genes of bacteriophage P1: Doc, which causes cell death on curing of prophage, and phd, which prevents host death when prophage is retained. J Mol Biol 233:414–428.
   PubMedGoogle Scholar
• Leplae R, Geeraerts D, Hallez R, Guglielmini J, Drèze P, Van Melderen L. 2011. Diversity of bacterial type II toxin-antitoxin systems: A comprehensive search and functional analysis of novel families. Nucleic Acids Res 39:5513–5525.
   PubMedGoogle Scholar
• Lewis K. 2010. Persister cells. Annu Rev Microbiol 64:357–372.
   PubMed Web of Science ®Google Scholar
• Li GY, Zhang Y, Chan MC, Mal TK, Hoeflich KP, Inouye M, Ikura M. 2006. Characterization of dual substrate binding sites in the homodimeric structure of Escherichia coli mRNA interferase MazF. J Mol Biol 357:139–150.
   Google Scholar
• Li GY, Zhang Y, Inouye M, Ikura M. 2008. Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module. J Mol Biol 380:107–119.
   Google Scholar
• Li GY, Zhang Y, Inouye M, Ikura M. 2009. Inhibitory mechanism of Escherichia coli RelE-RelB toxin-antitoxin module involves a helix displacement near an mRNA interferase active site. J Biol Chem 284:14628–14636.
   Google Scholar
• Lioy VS, Martín MT, Camacho AG, Lurz R, Antelmann H, Hecker M, Hitchin E, Ridge Y, Wells JM, Alonso JC. 2006. pSM19035-encoded ζ toxin induces stasis followed by death in a subpopulation of cells. Microbiology 152:2365–2379.
   Google Scholar
• Lioy VS, Rey O, Balsa D, Pellicer T, Alonso JC. 2010. A toxin-antitoxin module as a target for antimicrobial development. Plasmid 63:31–39.
   PubMed Web of Science ®Google Scholar
• Liu M, Zhang Y, Inouye M, Woychik NA. 2008. Bacterial addiction module toxin Doc inhibits translation elongation through its association with the 30S ribosomal subunit. Proc Natl Acad Sci USA 105:5885–5890.
   PubMed Web of Science ®Google Scholar
• Loris R, Dao-Thi MH, Bahassi EM, Van Melderen L, Poortmans F, Liddington R, Couturier M, Wyns L. 1999. Crystal structure of CcdB, a topoisomerase poison from E. coli. J Mol Biol 285:1667–1677.
   PubMed Web of Science ®Google Scholar
• Loris R, Marianovsky I, Lah J, Laeremans T, Engelberg-Kulka H, Glaser G, Muyldermans S, Wyns L. 2003. Crystal structure of the intrinsically flexible addiction antidote MazE. J Biol Chem 278:28252–28257.
   PubMed Web of Science ®Google Scholar
• Madl T, Van Melderen L, Mine N, Respondek M, Oberer M, Keller W, Khatai L, Zangger K. 2006. Structural basis for nucleic acid and toxin recognition of the bacterial antitoxin CcdA. J Mol Biol 364:170–185.
   Google Scholar
• Magnuson RD. 2007. Hypothetical functions of toxin-antitoxin systems. J Bacteriol 189:6089–6092.
   PubMed Web of Science ®Google Scholar
• Makarova KS, Wolf YI, Koonin EV. 2009. Comprehensive comparative-genomic analysis of type 2 toxin-antitoxin systems and related mobile stress response systems in prokaryotes. Biol Direct 4:19.
   Google Scholar
• Maki S, Takiguchi S, Miki T, Horiuchi T. 1992. Modulation of DNA supercoiling activity of Escherichia coli DNA gyrase by F plasmid proteins. Antagonistic actions of LetA (CcdA) and LetD (CcdB) proteins. J Biol Chem 267:12244–12251.
   Google Scholar
• Margolin W. 2009. Sculpting the bacterial cell. Curr Biol 19:R812–R822.
   Google Scholar
• Marianovsky I, Aizenman E, Engelberg-Kulka H, Glaser G. 2001. The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome. J Biol Chem 276:5975–5984.
   Google Scholar
• Masuda Y, Miyakawa K, Nishimura Y, Ohtsubo E. 1993. chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R100. J Bacteriol 175:6850–6856.
   PubMedGoogle Scholar
• Mattison K, Wilbur JS, So M, Brennan RG. 2006. Structure of FitAB from Neisseria gonorrhoeae bound to DNA reveals a tetramer of toxin-antitoxin heterodimers containing Pin domains and ribbon-helix-helix motifs. J Biol Chem 281:37942–37951.
   Google Scholar
• Meinhart A, Alonso JC, Sträter N, Saenger W. 2003. Crystal structure of the plasmid maintenance system ε/ζ: Functional mechanism of toxin ζ and inactivation by ε2 ζ2 complex formation. Proc Natl Acad Sci USA 100:1661–1666.
   PubMedGoogle Scholar
• Miallau L, Faller M, Chiang J, Arbing M, Guo F, Cascio D, Eisenberg D. 2009. Structure and proposed activity of a member of the VapBC family of toxin-antitoxin systems. VapBC-5 from Mycobacterium tuberculosis. J Biol Chem 284:276–283.
   Google Scholar
• Miki T, Park JA, Nagao K, Murayama N, Horiuchi T. 1992. Control of segregation of chromosomal DNA by sex factor F in Escherichia coli. Mutants of DNA gyrase subunit A suppress letD (ccdB)product growth inhibition. J Mol Biol 225:39–52.
   PubMed Web of Science ®Google Scholar
• Mine N, Guglielmini J, Wilbaux M, Van Melderen L. 2009. The decay of the chromosomally encoded ccdO157 toxin-antitoxin system in the Escherichia coli species. Genetics 181:1557–1566.
   Google Scholar
• Mitchell HL, Dashper SG, Catmull DV, Paolini RA, Cleal SM, Slakeski N, Tan KH, Reynolds EC. 2010. Treponema denticola biofilm-induced expression of a bacteriophage, toxin-antitoxin systems and transposases. Microbiology 156:774–788.
   PubMed Web of Science ®Google Scholar
• Monti MC, Hernández-Arriaga AM, Kamphuis MB, López-Villarejo J, Heck AJ, Boelens R, Díaz-Orejas R, van den Heuvel RH. 2007. Interactions of Kid-Kis toxin-antitoxin complexes with the parD operator-promoter region of plasmid R1 are piloted by the Kis antitoxin and tuned by the stoichiometry of Kid-Kis oligomers. Nucleic Acids Res 35:1737–1749.
   Google Scholar
• Moore SD, Sauer RT. 2007. The tmRNA system for translational surveillance and ribosome rescue. Annu Rev Biochem 76:101–124.
   PubMed Web of Science ®Google Scholar
• Motiejunaite R, Armalyte J, Markuckas A, Suziedeliene E. 2007. Escherichia coli dinJ-yafQ genes act as a toxin-antitoxin module. FEMS Microbiol Lett 268:112–119.
   PubMed Web of Science ®Google Scholar
• Moyed HS, Bertrand KP. 1983. hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. J Bacteriol 155:768–775.
   PubMed Web of Science ®Google Scholar
• Muñoz-Gómez AJ, Santos-Sierra S, Berzal-Herranz A, Lemonnier M, Díaz-Orejas R. 2004. Insights into the specificity of RNA cleavage by the Escherichia coli MazF toxin. FEBS Lett 567:316–320.
   PubMedGoogle Scholar
• Mutschler H, Gebhardt M, Shoeman RL, Meinhart A. 2011. A novel mechanism of programmed cell death in bacteria by toxin-antitoxin systems corrupts peptidoglycan synthesis. PLoS Biol 9:e1001033.
   PubMed Web of Science ®Google Scholar
• Mutschler H, Reinstein J, Meinhart A. 2010. Assembly dynamics and stability of the pneumococcal Epsilon Zeta antitoxin toxin (PezAT) system from Streptococcus pneumoniae. J Biol Chem 285:21797–21806.
   Google Scholar
• Nariya H, Inouye M. 2008. MazF, an mRNA interferase, mediates programmed cell death during multicellular Myxococcus development. Cell 132:55–66.
   Google Scholar
• Nehlsen K, Herrmann S, Zauers J, Hauser H, Wirth D. 2010. Toxin-antitoxin based transgene expression in mammalian cells. Nucleic Acids Res 38:e32.
   Google Scholar
• Neubauer C, Gao YG, Andersen KR, Dunham CM, Kelley AC, Hentschel J, Gerdes K, Ramakrishnan V, Brodersen DE. 2009. The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE. Cell 139:1084–1095.
   PubMed Web of Science ®Google Scholar
• Nieto C, Cherny I, Khoo SK, de Lacoba MG, Chan WT, Yeo CC, Gazit E, Espinosa M. 2007. The yefM-yoeB toxin-antitoxin systems of Escherichia coli and Streptococcus pneumoniae: Functional and structural correlation. J Bacteriol 189:1266–1278.
   Google Scholar
• Nöllmann M, Crisona NJ, Arimondo PB. 2007. Thirty years of Escherichia coli DNA gyrase: From in vivo function to single-molecule mechanism. Biochimie 89:490–499.
   Google Scholar
• Oberer M, Zangger K, Gruber K, Keller W. 2007. The solution structure of ParD, the antidote of the ParDE toxin antitoxin module, provides the structural basis for DNA and toxin binding. Protein Sci 16:1676–1688.
   Google Scholar
• Ogura T, Hiraga S. 1983. Mini-F plasmid genes that couple host cell division to plasmid proliferation. Proc Natl Acad Sci USA 80:4784–4788.
   PubMed Web of Science ®Google Scholar
• Overgaard M, Borch J, Gerdes K. 2009. RelB and RelE of Escherichia coli form a tight complex that represses transcription via the ribbon-helix-helix motif in RelB. J Mol Biol 394:183–196.
   Google Scholar
• Overgaard M, Borch J, Jørgensen MG, Gerdes K. 2008. Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity. Mol Microbiol 69:841–857.
   PubMed Web of Science ®Google Scholar
• Pandey DP, Gerdes K. 2005. Toxin-antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res 33:966–976.
   PubMed Web of Science ®Google Scholar
• Pecota DC, Wood TK. 1996. Exclusion of T4 phage by the hok/sok killer locus from plasmid R1. J Bacteriol 178:2044–2050.
   PubMed Web of Science ®Google Scholar
• Pedersen K, Gerdes K. 1999. Multiple hok genes on the chromosome of Escherichia coli. Mol Microbiol 32:1090–1102.
   PubMed Web of Science ®Google Scholar
• Pedersen K, Christensen SK, Gerdes K. 2002. Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins. Mol Microbiol 45:501–510.
   PubMed Web of Science ®Google Scholar
• Pedersen K, Zavialov AV, Pavlov MY, Elf J, Gerdes K, Ehrenberg M. 2003. The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site. Cell 112:131–140.
   PubMed Web of Science ®Google Scholar
• Pellegrini O, Mathy N, Gogos A, Shapiro L, Condon C. 2005. The Bacillus subtilis ydcDE operon encodes an endoribonuclease of the MazF/PemK family and its inhibitor. Mol Microbiol 56:1139–1148.
   PubMed Web of Science ®Google Scholar
• Pimentel B, Madine MA, de la Cueva-Méndez G. 2005. Kid cleaves specific mRNAs at UUACU sites to rescue the copy number of plasmid R1. EMBO J 24:3459–3469.
   Google Scholar
• Poulsen LK, Larsen NW, Molin S, Andersson P. 1989. A family of genes encoding a cell-killing function may be conserved in all gram-negative bacteria. Mol Microbiol 3:1463–1472.
   Google Scholar
• Price MN, Alm EJ, Arkin AP. 2005. Interruptions in gene expression drive highly expressed operons to the leading strand of DNA replication. Nucleic Acids Res 33:3224–3234.
   PubMed Web of Science ®Google Scholar
• Prysak MH, Mozdzierz CJ, Cook AM, Zhu L, Zhang Y, Inouye M, Woychik NA. 2009. Bacterial toxin YafQ is an endoribonuclease that associates with the ribosome and blocks translation elongation through sequence-specific and frame-dependent mRNA cleavage. Mol Microbiol 71:1071–1087.
   PubMed Web of Science ®Google Scholar
• Raleigh EA. 1992. Organization and function of the mcrBC genes of Escherichia coli K-12. Mol Microbiol 6:1079–1086.
   Google Scholar
• Ramage HR, Connolly LE, Cox JS. 2009. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: Implications for pathogenesis, stress responses, and evolution. PLoS Genet 5:e1000767.
   Google Scholar
• Ren D, Bedzyk LA, Thomas SM, Ye RW, Wood TK. 2004. Gene expression in Escherichia coli biofilms. Appl Microbiol Biotechnol 64:515–524.
   PubMed Web of Science ®Google Scholar
• Roberts RC, Burioni R, Helinski DR. 1990. Genetic characterization of the stabilizing functions of a region of broad-host-range plasmid RK2. J Bacteriol 172:6204–6216.
   Google Scholar
• Roberts RC, Ström AR, Helinski DR. 1994. The parDE operon of the broad-host-range plasmid RK2 specifies growth inhibition associated with plasmid loss. J Mol Biol 237:35–51.
   Google Scholar
• Robson J, McKenzie JL, Cursons R, Cook GM, Arcus VL. 2009. The vapBC operon from Mycobacterium smegmatis is an autoregulated toxin-antitoxin module that controls growth via inhibition of translation. J Mol Biol 390:353–367.
   PubMed Web of Science ®Google Scholar
• Rotem E, Loinger A, Ronin I, Levin-Reisman I, Gabay C, Shoresh N, Biham O, Balaban NQ. 2010. Regulation of phenotypic variability by a threshold-based mechanism underlies bacterial persistence. Proc Natl Acad Sci USA 107:12541–12546.
   PubMed Web of Science ®Google Scholar
• Saavedra De Bast M, Mine N, Van Melderen L. 2008. Chromosomal toxin-antitoxin systems may act as anti-addiction modules. J Bacteriol 190:4603–4609.
   PubMed Web of Science ®Google Scholar
• Sat B, Hazan R, Fisher T, Khaner H, Glaser G, Engelberg-Kulka H. 2001. Programmed cell death in Escherichia coli: Some antibiotics can trigger mazEF lethality. J Bacteriol 183:2041–2045.
   PubMed Web of Science ®Google Scholar
• Sat B, Reches M, Engelberg-Kulka H. 2003. The Escherichia coli mazEF suicide module mediates thymineless death. J Bacteriol 185:1803–1807.
   PubMedGoogle Scholar
• Schmidt O, Schuenemann VJ, Hand NJ, Silhavy TJ, Martin J, Lupas AN, Djuranovic S. 2007. prlF and yhaV encode a new toxin-antitoxin system in Escherichia coli. J Mol Biol 372:894–905.
   Google Scholar
• Schneider WM, Inouye M, Montelione GT, Roth MJ. 2009. Independently inducible system of gene expression for condensed single protein production (cSPP) suitable for high efficiency isotope enrichment. J Struct Funct Genomics 10:219–225.
   PubMedGoogle Scholar
• Schumacher MA, Piro KM, Xu W, Hansen S, Lewis K, Brennan RG. 2009. Molecular mechanisms of HipA-mediated multidrug tolerance and its neutralization by HipB. Science 323:396–401.
   PubMed Web of Science ®Google Scholar
• Sengupta M, Austin S. 2011. The prevalence and significance of plasmid maintenance functions in the virulence plasmids of pathogenic bacteria. Infect Immun 79:2502–2509.
   PubMedGoogle Scholar
• Shimazu T, Degenhardt K, Nur-E-Kamal A, Zhang J, Yoshida T, Zhang Y, Mathew R, White E, Inouye M. 2007. NBK/BIK antagonizes MCL-1 and BCL-XL and activates BAK-mediated apoptosis in response to protein synthesis inhibition. Genes Dev 21:929–941.
   PubMedGoogle Scholar
• Shinohara M, Guo JX, Mori M, Nakashima T, Takagi H, Nishimoto E, Yamashita S, Tsumoto K, Kakuta Y, Kimura M. 2010. The structural mechanism of the inhibition of archaeal RelE toxin by its cognate RelB antitoxin. Biochem Biophys Res Commun 400:346–351.
   Google Scholar
• Simic M, De Jonge N, Loris R, Vesnaver G, Lah J. 2009. Driving forces of gyrase recognition by the addiction toxin CcdB. J Biol Chem 284:20002–20010.
   Google Scholar
• Singletary LA, Gibson JL, Tanner EJ, McKenzie GJ, Lee PL, Gonzalez C, Rosenberg SM. 2009. An SOS-regulated type 2 toxin-antitoxin system. J Bacteriol 191:7456–7465.
   PubMedGoogle Scholar
• Smith AB, Maxwell A. 2006. A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site. Nucleic Acids Res 34:4667–4676.
   Google Scholar
• Stieber D, Gabant P, Szpirer C. 2008. The art of selective killing: Plasmid toxin/antitoxin systems and their technological applications. BioTechniques 45:344–346.
   PubMed Web of Science ®Google Scholar
• Suzuki M, Roy R, Zheng H, Woychik N, Inouye M. 2006. Bacterial bioreactors for high yield production of recombinant protein. J Biol Chem 281:37559–37565.
   PubMed Web of Science ®Google Scholar
• Suzuki M, Zhang J, Liu M, Woychik NA, Inouye M. 2005. Single protein production in living cells facilitated by an mRNA interferase. Mol Cell 18:253–261.
   Google Scholar
• Syed MA, Koyanagi S, Sharma E, Jobin MC, Yakunin AF, Lévesque CM. 2011. The chromosomal mazEF locus of Streptococcus mutans encodes a functional type II toxin-antitoxin addiction system. J Bacteriol 193:1122–1130.
   PubMed Web of Science ®Google Scholar
• Szekeres S, Dauti M, Wilde C, Mazel D, Rowe-Magnus DA. 2007. Chromosomal toxin-antitoxin loci can diminish large-scale genome reductions in the absence of selection. Mol Microbiol 63:1588–1605.
   Google Scholar
• Takagi H, Kakuta Y, Okada T, Yao M, Tanaka I, Kimura M. 2005. Crystal structure of archaeal toxin-antitoxin RelE-RelB complex with implications for toxin activity and antitoxin effects. Nat Struct Mol Biol 12:327–331.
   PubMedGoogle Scholar
• Tan Q, Awano N, Inouye M. 2011. YeeV is an Escherichia coli toxin that inhibits cell division by targeting the cytoskeleton proteins, FtsZ and MreB. Mol Microbiol 79:109–118.
   PubMed Web of Science ®Google Scholar
• Tian QB, Ohnishi M, Tabuchi A, Terawaki Y. 1996. A new plasmid-encoded proteic killer gene system: Cloning, sequencing, and analyzing hig locus of plasmid Rts1. Biochem Biophys Res Commun 220:280–284.
   Google Scholar
• Tobes R, Pareja E. 2006. Bacterial repetitive extragenic palindromic sequences are DNA targets for Insertion Sequence elements. BMC Genomics 7:62.
   Google Scholar
• Trifonov EN, Frenkel ZM. 2009. Evolution of protein modularity. Curr Opin Struct Biol 19:335–340.
   PubMed Web of Science ®Google Scholar
• Tsilibaris V, Maenhaut-Michel G, Mine N, Van Melderen L. 2007. What is the benefit to Escherichia coli of having multiple toxin-antitoxin systems in its genome? J Bacteriol 189:6101–6108.
   PubMed Web of Science ®Google Scholar
• Tsuchimoto S, Nishimura Y, Ohtsubo E. 1992. The stable maintenance system pem of plasmid R100: Degradation of PemI protein may allow PemK protein to inhibit cell growth. J Bacteriol 174:4205–4211.
   Google Scholar
• Tsuchimoto S, Ohtsubo H, Ohtsubo E. 1988. Two genes, pemK and pemI, responsible for stable maintenance of resistance plasmid R100. J Bacteriol 170:1461–1466.
   Google Scholar
• Vaiphei ST, Mao L, Shimazu T, Park JH, Inouye M. 2010. Use of amino acids as inducers for high-level protein expression in the single-protein production system. Appl Environ Microbiol 76:6063–6068.
   Google Scholar
• Van Melderen L. 2002. Molecular interactions of the CcdB poison with its bacterial target, the DNA gyrase. Int J Med Microbiol 291:537–544.
   PubMed Web of Science ®Google Scholar
• Van Melderen L. 2010. Toxin-antitoxin systems: Why so many, what for? Curr Opin Microbiol 13:781–785.
   PubMed Web of Science ®Google Scholar
• Van Melderen L, Bernard P, Couturier M. 1994. Lon-dependent proteolysis of CcdA is the key control for activation of CcdB in plasmid-free segregant bacteria. Mol Microbiol 11:1151–1157.
   PubMed Web of Science ®Google Scholar
• Van Melderen L, Saavedra De Bast M. 2009. Bacterial toxin-antitoxin systems: More than selfish entities? PLoS Genet 5:e1000437.
   Web of Science ®Google Scholar
• Van Melderen L, Thi MH, Lecchi P, Gottesman S, Couturier M, Maurizi MR. 1996. ATP-dependent degradation of CcdA by Lon protease. Effects of secondary structure and heterologous subunit interactions. J Biol Chem 271:27730–27738.
   Google Scholar
• Welch RA, Burland V, Plunkett G 3rd, Redford P, Roesch P, Rasko D, Buckles EL, Liou SR, Boutin A, Hackett J, Stroud D, Mayhew GF, Rose DJ, Zhou S, Schwartz DC, Perna NT, Mobley HL, Donnenberg MS, Blattner FR. 2002. Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli. Proc Natl Acad Sci USA 99:17020–17024.
   PubMed Web of Science ®Google Scholar
• Wilbaux M, Mine N, Guérout AM, Mazel D, Van Melderen L. 2007. Functional interactions between coexisting toxin-antitoxin systems of the ccd family in Escherichia coli O157:H7. J Bacteriol 189:2712–2719.
   Google Scholar
• Williams JJ, Hergenrother PJ. 2008. Exposing plasmids as the Achilles′ heel of drug-resistant bacteria. Curr Opin Chem Biol 12:389–399.
   PubMed Web of Science ®Google Scholar
• Winther KS, Gerdes K. 2009. Ectopic production of VapCs from Enterobacteria inhibits translation and trans-activates YoeB mRNA interferase. Mol Microbiol 72:918–930.
   Google Scholar
• Winther KS, Gerdes K. 2011. Enteric virulence associated protein VapC inhibits translation by cleavage of initiator tRNA. Proc Natl Acad Sci USA 108:7403–7407.
   PubMed Web of Science ®Google Scholar
• Wood TK. 2009. Insights on Escherichia coli biofilm formation and inhibition from whole-transcriptome profiling. Environ Microbiol 11:1–15.
   PubMed Web of Science ®Google Scholar
• Wozniak RA, Waldor MK. 2009. A toxin-antitoxin system promotes the maintenance of an integrative conjugative element. PLoS Genet 5:e1000439.
   PubMed Web of Science ®Google Scholar
• Yamaguchi Y, Inouye M. 2009. mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems. Prog Mol Biol Transl Sci 85:467–500.
   PubMed Web of Science ®Google Scholar
• Yamamoto TA, Gerdes K, Tunnacliffe A. 2002. Bacterial toxin RelE induces apoptosis in human cells. FEBS Lett 519:191–194.
   PubMed Web of Science ®Google Scholar
• Yang M, Gao C, Wang Y, Zhang H, He ZG. 2010. Characterization of the interaction and cross-regulation of three Mycobacterium tuberculosis RelBE modules. PLoS ONE 5:e10672.
   PubMedGoogle Scholar
• Yarmolinsky MB. 1995. Programmed cell death in bacterial populations. Science 267:836–837.
   PubMed Web of Science ®Google Scholar
• Yoshizumi S, Zhang Y, Yamaguchi Y, Chen L, Kreiswirth BN, Inouye M. 2009. Staphylococcus aureus YoeB homologues inhibit translation initiation. J Bacteriol 191:5868–5872.
   Google Scholar
• Yuan J, Sterckx Y, Mitchenall LA, Maxwell A, Loris R, Waldor MK. 2010. Vibrio cholerae ParE2 poisons DNA gyrase via a mechanism distinct from other gyrase inhibitors. J Biol Chem 285:40397–40408.
   PubMedGoogle Scholar
• Yuan J, Yamaichi Y, Waldor MK. 2011. The three Vibrio cholerae chromosome II-encoded ParE toxins degrade chromosome I following loss of chromosome II. J Bacteriol 193:611–619.
   Google Scholar
• Zhang J, Zhang Y, Zhu L, Suzuki M, Inouye M. 2004. Interference of mRNA function by sequence-specific endoribonuclease PemK. J Biol Chem 279:20678–20684.
   Google Scholar
• Zhang Y, Inouye M. 2009. The inhibitory mechanism of protein synthesis by YoeB, an Escherichia coli toxin. J Biol Chem 284:6627–6638.
   Google Scholar
• Zhang Y, Inouye M. 2011. RatA (YfjG), an Escherichia coli toxin, inhibits 70S ribosome association to block translation initiation. Mol Microbiol 79:1418–1429.
   Google Scholar
• Zhang Y, Yamaguchi Y, Inouye M. 2009. Characterization of YafO, an Escherichia coli toxin. J Biol Chem 284:25522–25531.
   Google Scholar
• Zhang Y, Zhang J, Hara H, Kato I, Inouye M. 2005a. Insights into the mRNA cleavage mechanism by MazF, an mRNA interferase. J Biol Chem 280:3143–3150.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhang J, Hoeflich KP, Ikura M, Qing G, Inouye M. 2003. MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli. Mol Cell 12:913–923.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhu L, Zhang J, Inouye M. 2005b. Characterization of ChpBK, an mRNA interferase from Escherichia coli. J Biol Chem 280:26080–26088.
   Google Scholar
• Zhao X, Magnuson RD. 2005. Percolation of the phd repressor-operator interface. J Bacteriol 187:1901–1912.
   Google Scholar
• Zhu L, Inoue K, Yoshizumi S, Kobayashi H, Zhang Y, Ouyang M, Kato F, Sugai M, Inouye M. 2009. Staphylococcus aureus MazF specifically cleaves a pentad sequence, UACAU, which is unusually abundant in the mRNA for pathogenic adhesive factor SraP. J Bacteriol 191:3248–3255.
   Google Scholar
• Zhu L, Phadtare S, Nariya H, Ouyang M, Husson RN, Inouye M. 2008. The mRNA interferases, MazF-mt3 and MazF-mt7 from Mycobacterium tuberculosis target unique pentad sequences in single-stranded RNA. Mol Microbiol 69:559–569.
   Google Scholar
• Zhu L, Sharp JD, Kobayashi H, Woychik NA, Inouye M. 2010. Noncognate Mycobacterium tuberculosis toxin-antitoxins can physically and functionally interact. J Biol Chem 285:39732–39738.
   PubMed Web of Science ®Google Scholar
• Zhu L, Zhang Y, Teh JS, Zhang J, Connell N, Rubin H, Inouye M. 2006. Characterization of mRNA interferases from Mycobacterium tuberculosis. J Biol Chem 281:18638–18643.
   Google Scholar
• Zielenkiewicz U, Ceglowski P. 2005. The toxin-antitoxin system of the streptococcal plasmid pSM19035. J Bacteriol 187:6094–6105.
   Google Scholar