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Prokaryotic Toxin-Antitoxins pp 267–294Cite as

Type II Toxin-Antitoxin Loci Encoded by Plasmids

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Abstract

Toxin–antitoxin (TA) loci were initially identified as auxiliary plasmid maintenance modules (Gerdes 2000). We review a few type II TA systems of the early list that are found in plasmids of Gram-negative bacteria and that have been more extensively characterized. These include the ccd system of plasmid F, the kis-kid system of plasmid R1, the higBA system of plasmid Rts1, and the parDE system of plasmid RK2. We also review two systems found in plasmids of Gram-positive bacteria: the ω-ε-ζ system found in a plasmid pSM19035 of Streptococcus pyogenes and the axe-txe system found in pRUM, a multidrug resistant factor of Enterococcus faecium. Most of these systems have been analyzed both at the functional and structural levels and on the whole they provide an insight on the essential features, diversity, relationships, and relevance of type II TA loci.

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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. Molecular Microbiology, 41, 73–82.

    PubMed  CAS  Google Scholar 

  • Bahassi, E. M., Salmon, M. A., Van Melderen, L., Bernard, P., & Couturier, M. (1995). F plasmid CcdB killer protein: ccdB gene mutants coding for non-cytotoxic proteins which retain their regulatory functions. Molecular Microbiology, 15, 1031–1037.

    PubMed  CAS  Google Scholar 

  • Bahassi, E. M., O’Dea, M. H., 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. The Journal of Biological Chemistry, 274, 10936–10944.

    PubMed  CAS  Google Scholar 

  • Barbosa, L. C., Garrido, S. S., Garcia, A., Delfino, D. B., & Marchetto, R. (2010). Function inferences from a molecular structural model of bacterial ParE toxin. Bioinformation, 4, 438–440.

    PubMed  Google Scholar 

  • Bernard, P., & Couturier, M. (1991). The 41 carboxy-terminal residues of the miniF plasmid CcdA protein are sufficient to antagonize the killer activity of the CcdB protein. Molecular and General Genetics, 226, 297–304.

    PubMed  CAS  Google Scholar 

  • Bernard, P., & Couturier, M. (1992). Cell killing by the F plasmid CcdB protein involves poisoning of DNA-topoisomerase II complexes. Journal of Molecular Biology, 226, 735–745.

    PubMed  CAS  Google Scholar 

  • Bernard, P., Kezdy, K. E., Van Melderen, L., Steyaert, J., Wyns, L., Pato, M. L., et al. (1993). The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by gyrase. Journal of Molecular Biology, 234, 534–541.

    PubMed  CAS  Google Scholar 

  • Bjorkeng, E., Rasmussen, G., Sundsfjord, A., Sjoberg, L., Hegstad, K., & Soderquist, B. (2011). Clustering of polyclonal VanB-type vancomycin-resistant Enterococcus faecium in a low-endemic area was associated with CC17-genogroup strains harbouring transferable vanB2-Tn5382 and pRUM-like repA containing plasmids with axe-txe plasmid addiction systems. Apmis, 119, 247–258.

    PubMed  Google Scholar 

  • Blower, T. R., Salmond, G. P., & Luisi, B. F. (2011). Balancing at survival’s edge: The structure and adaptive benefits of prokaryotic toxin–antitoxin partners. Current Opinion in Structural Biology, 21, 109–118.

    PubMed  CAS  Google Scholar 

  • Bordes, P., Cirinesi, A. M., Ummels, R., Sala, A., Sakr, S., Bitter, W., et al. (2011). SecB-like chaperone controls a toxin–antitoxin stress-responsive system in Mycobacterium tuberculosis. Proceedings of the National Academy of Sciences of the United States of America, 108, 8438–8443.

    PubMed  CAS  Google Scholar 

  • Bravo, A., de Torrontegui, G., & Diaz, 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. Molecular and General Genetics, 210, 101–110.

    PubMed  CAS  Google Scholar 

  • Bravo, A., Ortega, S., de Torrontegui, G., & Diaz, R. (1988). Killing of Escherichia coli cells modulated by components of the stability system ParD of plasmid R1. Molecular and General Genetics, 215, 146–151.

    PubMed  CAS  Google Scholar 

  • Breg, J. N., van Opheusden, J. H., Burgering, M. J., Boelens, R., & Kaptein, R. (1990). Structure of Arc repressor in solution: Evidence for a family of beta-sheet DNA-binding proteins. Nature, 346, 586–589.

    PubMed  CAS  Google Scholar 

  • Brown, J. S., Gilliland, S. M., Spratt, B. G., & Holden, D. W. (2004). A locus contained within a variable region of pneumococcal pathogenicity island 1 contributes to virulence in mice. Infection and Immunity, 72, 1587–1593.

    PubMed  CAS  Google Scholar 

  • Budde, P. P., Davis, B. M., Yuan, J., & Waldor, M. K. (2007). Characterization of a higBA toxin–antitoxin locus in Vibrio cholerae. Journal of Bacteriology, 189, 491–500.

    PubMed  CAS  Google Scholar 

  • Buts, L., Lah, J., Dao-Thi, M. H., Wyns, L., & Loris, R. (2005). Toxin–antitoxin modules as bacterial metabolic stress managers. Trends in Biochemical Sciences, 30, 672–679.

    PubMed  CAS  Google Scholar 

  • Camacho, A. G., Misselwitz, R., Behlke, J., Ayora, S., Welfle, K., Meinhart, A., et al. (2002). In vitro and in vivo stability of the epsilon2zeta2 protein complex of the broad host-range Streptococcus pyogenes pSM19035 addiction system. Biological Chemistry, 383, 1701–1713.

    PubMed  CAS  Google Scholar 

  • Ceglowski, P., Boitsov, A., Chai, S., & Alonso, J. C. (1993a). Analysis of the stabilization system of pSM19035-derived plasmid pBT233 in Bacillus subtilis. Gene, 136, 1–12.

    PubMed  CAS  Google Scholar 

  • Ceglowski, P., Boitsov, A., Karamyan, N., Chai, S., & Alonso, J. C. (1993b). Characterization of the effectors required for stable inheritance of Streptococcus pyogenes pSM19035-derived plasmids in Bacillus subtilis. Molecular and General Genetics, 241, 579–585.

    PubMed  CAS  Google Scholar 

  • Christensen-Dalsgaard, M., & Gerdes, K. (2006). Two higBA loci in the Vibrio cholerae superintegron encode mRNA cleaving enzymes and can stabilize plasmids. Molecular Microbiology, 62, 397–411.

    PubMed  CAS  Google Scholar 

  • Cooper, T. F., & Heinemann, J. A. (2000). Postsegregational killing does not increase plasmid stability but acts to mediate the exclusion of competing plasmids. Proceedings of the National Academy of Sciences of the United States of America, 97, 12643–12648.

    PubMed  CAS  Google Scholar 

  • Couturier, M., Bahassi M. el & Van Melderen, L. (1998) Bacterial death by DNA gyrase poisoning. Trends in Microbiology 6, 269–275.

    Google Scholar 

  • Critchlow, S. E., O’Dea, M. H., Howells, A. J., 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. Journal of Molecular Biology, 273, 826–839.

    PubMed  CAS  Google Scholar 

  • Dalton, K. M., & Crosson, S. (2010). A conserved mode of protein recognition and binding in a ParD–ParE toxin–antitoxin complex. Biochemistry, 49, 2205–2216.

    PubMed  CAS  Google Scholar 

  • Dao-Thi, M. H., Charlier, D., Loris, R., Maes, D., Messens, J., Wyns, L., et al. (2002). Intricate interactions within the ccd plasmid addiction system. The Journal of Biological Chemistry, 277, 3733–3742.

    PubMed  CAS  Google Scholar 

  • Dao-Thi, M. H., Van Melderen, L., De Genst, E., Afif, H., Buts, L., Wyns, L., et al. (2005). Molecular basis of gyrase poisoning by the addiction toxin CcdB. Journal of Molecular Biology, 348, 1091–1102.

    PubMed  CAS  Google Scholar 

  • Davis, T. L., Helinski, D. R., & Roberts, R. C. (1992). Transcription and autoregulation of the stabilizing functions of broad-host-range plasmid RK2 in Escherichia coli, Agrobacterium tumefaciens and Pseudomonas aeruginosa. Molecular Microbiology, 6, 1981–1994.

    PubMed  CAS  Google Scholar 

  • De Jonge, N., Garcia-Pino, A., Buts, L., Haesaerts, S., Charlier, D., Zangger, K., et al. (2009). Rejuvenation of CcdB-poisoned gyrase by an intrinsically disordered protein domain. Molecular Cell, 35, 154–163.

    PubMed  Google Scholar 

  • de la Hoz, A. B., Ayora, S., Sitkiewicz, I., Fernandez, S., Pankiewicz, R., Alonso, J. C., et al. (2000). Plasmid copy-number control and better-than-random segregation genes of pSM19035 share a common regulator. Proceedings of the National Academy of Sciences of the United States of America, 97, 728–733.

    PubMed  Google Scholar 

  • de la Hoz, A. B., Pratto, F., Misselwitz, R., Speck, C., Weihofen, W., Welfle, K., et al. (2004). Recognition of DNA by omega protein from the broad-host range Streptococcus pyogenes plasmid pSM19035: analysis of binding to operator DNA with one to four heptad repeats. Nucleic Acids Research, 32, 3136–3147.

    PubMed  Google Scholar 

  • De Lano, W. L. (2002). The Pymol Molecular Graphics System. San Carlos: De Lano Scientific.

    Google Scholar 

  • del Solar, G., Hernandez-Arriaga, A. M., Gomis-Ruth, F. X., Coll, M., & Espinosa, M. (2002). A genetically economical family of plasmid-encoded transcriptional repressors involved in control of plasmid copy number. Journal of Bacteriology, 184, 4943–4951.

    PubMed  Google Scholar 

  • Diago-Navarro, E., Kamphuis, M. B., Boelens, R., Barendregt, A., Heck, A. J., van den Heuvel, R. H., et al. (2009). A mutagenic analysis of the RNase mechanism of the bacterial Kid toxin by mass spectrometry. The FEBS Journal, 276, 4973–4986.

    PubMed  CAS  Google Scholar 

  • Diago-Navarro, E., Hernandez-Arriaga, A. M., Lopez-Villarejo, J., Munoz-Gomez, A. J., Kamphuis, M. B., Boelens, R., et al. (2010). parD toxin–antitoxin system of plasmid R1—basic contributions, biotechnological applications and relationships with closely-related toxin–antitoxin systems. The FEBS Journal, 277, 3097–3117.

    PubMed  CAS  Google Scholar 

  • Dixon, J. M., & Lipinski, A. E. (1972). Resistance of group A beta-hemolytic streptococci to lincomycin and erythromycin. Antimicrobial Agents and Chemotherapy, 1, 333–339.

    PubMed  CAS  Google Scholar 

  • Eberl, L., Givskov, M., & Schwab, H. (1992). The divergent promoters mediating transcription of the par locus of plasmid RP4 are subject to autoregulation. Molecular Microbiology, 6, 1969–1979.

    PubMed  CAS  Google Scholar 

  • Fiebig, A., Castro Rojas, C. M., Siegal-Gaskins, D., & Crosson, S. (2010). Interaction specificity, toxicity and regulation of a paralogous set of ParE/RelE-family toxin–antitoxin systems. Molecular Microbiology, 77, 236–251.

    PubMed  CAS  Google Scholar 

  • Fineran, P. C., Blower, T. R., Foulds, I. J., Humphreys, D. P., Lilley, K. S., & Salmond, G. P. (2009). The phage abortive infection system, ToxIN, functions as a protein-RNA toxin–antitoxin pair. Proceedings of the National Academy of Sciences of the United States of America, 106, 894–899.

    PubMed  CAS  Google Scholar 

  • Francuski, D., & Saenger, W. (2009). Crystal structure of the antitoxin–toxin protein complex RelB–RelE from Methanococcus jannaschii. Journal of Molecular Biology, 393, 898–908.

    PubMed  CAS  Google Scholar 

  • Garcia-Pino, A., Balasubramanian, S., Wyns, L., Gazit, E., De Greve, H., Magnuson, R. D., et al. (2010). Allostery and intrinsic disorder mediate transcription regulation by conditional cooperativity. Cell, 142, 101–111.

    PubMed  CAS  Google Scholar 

  • Gerdes, K. (2000). Toxin–antitoxin modules may regulate synthesis of macromolecules during nutritional stress. Journal of Bacteriology, 182, 561–572.

    PubMed  CAS  Google Scholar 

  • Gerdes, K., Rasmussen, P. B., & Molin, S. (1986). Unique type of plasmid maintenance function: Postsegregational killing of plasmid-free cells. Proceedings of the National Academy of Sciences of the United States of America, 83, 3116–3120.

    PubMed  CAS  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. Molecular Microbiology, 47, 1419–1432.

    PubMed  CAS  Google Scholar 

  • Gronlund, H., & Gerdes, K. (1999). Toxin–antitoxin systems homologous with relBE of Escherichia coli plasmid P307 are ubiquitous in prokaryotes. Journal of Molecular Biology, 285, 1401–1416.

    PubMed  CAS  Google Scholar 

  • Halvorsen, E.M., Williams, J.J., Bhimani, A.J., Billings, E.A., & Hergenrother, P.J. (2011) Txe, an endoribonuclease of the enterococcal Axe-Txe toxin–antitoxin system, cleaves mRNA and inhibits protein synthesis. Microbiology (Reading, England) 157, 387–397.

    Google Scholar 

  • Hargreaves, D., Santos-Sierra, S., Giraldo, R., Sabariegos-Jareno, R., de la Cueva-Mendez, G., Boelens, R., et al. (2002). Structural and functional analysis of the kid toxin protein from E. coli plasmid R1. Structure, 10, 1425–1433.

    PubMed  CAS  Google Scholar 

  • Hayes, F. (1998). A family of stability determinants in pathogenic bacteria. Journal of Bacteriology, 180, 6415–6418.

    PubMed  CAS  Google Scholar 

  • Hurley, J. M., & Woychik, N. A. (2009). Bacterial toxin HigB associates with ribosomes and mediates translation-dependent mRNA cleavage at A-rich sites. The Journal of Biological Chemistry, 284, 18605–18613.

    PubMed  CAS  Google Scholar 

  • Jaffe, A., Ogura, T., & Hiraga, S. (1985). Effects of the ccd function of the F plasmid on bacterial growth. Journal of Bacteriology, 163, 841–849.

    PubMed  CAS  Google Scholar 

  • Jensen, R. B., Grohmann, E., Schwab, H., Diaz-Orejas, R., & Gerdes, K. (1995). Comparison of ccd of F, parDE of RP4, and parD of R1 using a novel conditional replication control system of plasmid R1. Molecular Microbiology, 17, 211–220.

    PubMed  CAS  Google Scholar 

  • Jiang, Y., Pogliano, J., Helinski, D. R., & Konieczny, I. (2002). ParE toxin encoded by the broad-host-range plasmid RK2 is an inhibitor of Escherichia coli gyrase. Molecular Microbiology, 44, 971–979.

    PubMed  CAS  Google Scholar 

  • Johnson, E. P., Strom, A. R., & Helinski, D. R. (1996). Plasmid RK2 toxin protein ParE: Purification and interaction with the ParD antitoxin protein. Journal of Bacteriology, 178, 1420–1429.

    PubMed  CAS  Google Scholar 

  • Kamada, K., & Hanaoka, F. (2005). Conformational change in the catalytic site of the ribonuclease YoeB toxin by YefM antitoxin. Molecular Cell, 19, 497–509.

    PubMed  CAS  Google Scholar 

  • Kamada, K., Hanaoka, F., & Burley, S. K. (2003). Crystal structure of the MazE/MazF complex: Molecular bases of antidote-toxin recognition. Molecular Cell, 11, 875–884.

    PubMed  CAS  Google Scholar 

  • Kamphuis, M. B., Bonvin, A. M., Monti, M. C., Lemonnier, M., Munoz-Gomez, A., van den Heuvel, R. H., et al. (2006). Model for RNA binding and the catalytic site of the RNase Kid of the bacterial parD toxin–antitoxin system. Journal of Molecular Biology, 357, 115–126.

    PubMed  CAS  Google Scholar 

  • Kamphuis, M. B., Monti, M. C., van den Heuvel, R. H., Santos-Sierra, S., Folkers, G. E., Lemonnier, M., et al. (2007). Interactions between the toxin Kid of the bacterial parD system and the antitoxins Kis and MazE. Proteins, 67, 219–231.

    PubMed  CAS  Google Scholar 

  • Klare, I., Heier, H., Claus, H., Bohme, G., Marin, S., Seltmann, G., Hakenbeck, R., Antanassova, V., & Witte, W. (1995) Enterococcus faecium strains with vanA-mediated high-level glycopeptide resistance isolated from animal foodstuffs and fecal samples of humans in the community. Microbial Drug Resistance (Larchmont, N.Y) 1, 265–272.

    Google Scholar 

  • Kuhn, I., Iversen, A., Finn, M., Greko, C., Burman, L. G., Blanch, A. R., et al. (2005). Occurrence and relatedness of vancomycin-resistant enterococci in animals, humans, and the environment in different European regions. Applied and Environmental Microbiology, 71, 5383–5390.

    PubMed  CAS  Google Scholar 

  • Lehnherr, H., Maguin, E., Jafri, S., & Yarmolinsky, M. B. (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. Journal of Molecular Biology, 233, 414–428.

    PubMed  CAS  Google Scholar 

  • Leplae, R., Geeraerts, D., Hallez, R., Guglielmini, J., Dreze, P., & Van Melderen, L. (2011). Diversity of bacterial type II toxin–antitoxin systems: A comprehensive search and functional analysis of novel families. Nucleic Acids Research, 39, 5513–5525.

    PubMed  CAS  Google Scholar 

  • Li, G. Y., Zhang, Y., Inouye, M., & Ikura, M. (2008). Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module. Journal of Molecular Biology, 380, 107–119.

    PubMed  CAS  Google Scholar 

  • Lioy, V.S., Martin, M.T., Camacho, A.G., Lurz, R., Antelmann, H., Hecker, M., Hitchin, E., Ridge, Y., Wells, J.M., & Alonso, J.C. (2006) pSM19035-encoded zeta toxin induces stasis followed by death in a subpopulation of cells. Microbiology (Reading, England) 152, 2365–2379.

    Google Scholar 

  • Lioy, V. S., Pratto, F., de la Hoz, A. B., Ayora, S., & Alonso, J. C. (2010). Plasmid pSM19035, a model to study stable maintenance in Firmicutes. Plasmid, 64, 1–17.

    PubMed  CAS  Google Scholar 

  • Lopez-Villarejo, J., Diago-Navarro, E., Hernandez-Arriaga, A.M., & Diaz-Orejas, R. (2012) Kis antitoxin couples plasmid R1 replication and parD (kis,kid) maintenance modules. Plasmid, 67, 118–127.

    PubMed  CAS  Google Scholar 

  • Loris, R., Dao-Thi, M. H., Bahassi, E. M., Van Melderen, L., Poortmans, F., Liddington, R., et al. (1999). Crystal structure of CcdB, a topoisomerase poison from E. coli. Journal of Molecular Biology, 285, 1667–1677.

    PubMed  CAS  Google Scholar 

  • Madl, T., Van Melderen, L., Mine, N., Respondek, M., Oberer, M., Keller, W., et al. (2006). Structural basis for nucleic acid and toxin recognition of the bacterial antitoxin CcdA. Journal of Molecular Biology, 364, 170–185.

    PubMed  CAS  Google Scholar 

  • Maki, S., Takiguchi, S., Horiuchi, T., Sekimizu, K., & Miki, T. (1996). Partner switching mechanisms in inactivation and rejuvenation of Escherichia coli DNA gyrase by F plasmid proteins LetD (CcdB) and LetA (CcdA). Journal of Molecular Biology, 256, 473–482.

    PubMed  CAS  Google Scholar 

  • Maxwell, A. (1997). DNA gyrase as a drug target. Trends in Microbiology, 5, 102–109.

    PubMed  CAS  Google Scholar 

  • Meinhart, A., Alonso, J. C., Strater, N., & Saenger, W. (2003). Crystal structure of the plasmid maintenance system epsilon/zeta: functional mechanism of toxin zeta and inactivation by epsilon 2 zeta 2 complex formation. Proceedings of the National Academy of Sciences of the United States of America, 100, 1661–1666.

    PubMed  CAS  Google Scholar 

  • Miki, T., Park, J. A., 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. Journal of Molecular Biology, 225, 39–52.

    PubMed  CAS  Google Scholar 

  • Monti, M. C., Hernandez-Arriaga, A. M., Kamphuis, M. B., Lopez-Villarejo, J., Heck, A. J., Boelens, R., et al. (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 Research, 35, 1737–1749.

    PubMed  CAS  Google Scholar 

  • Moritz, E. M., & Hergenrother, P. J. (2007). Toxin–antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci. Proceedings of the National Academy of Sciences of the United States of America, 104, 311–316.

    PubMed  CAS  Google Scholar 

  • Muñoz-Gomez, A. J., Lemonnier, M., Santos-Sierra, S., Berzal-Herranz, A., & Diaz-Orejas, R. (2005). RNase/anti-RNase activities of the bacterial parD toxin–antitoxin system. Journal of Bacteriology, 187, 3151–3157.

    PubMed  Google Scholar 

  • Murayama, K., Orth, P., de la Hoz, A. B., Alonso, J. C., & Saenger, W. (2001). Crystal structure of omega transcriptional repressor encoded by Streptococcus pyogenes plasmid pSM19035 at 1.5 Å resolution. Journal of Molecular Biology, 314, 789–796.

    PubMed  CAS  Google Scholar 

  • Mutschler, H., & Meinhart, A. (2011) Epsilon/zeta systems: Their role in resistance, virulence, and their potential for antibiotic development. Journal of Molecular Medicine (Berlin, Germany) 89, 1183–1194.

    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. The Journal of Biological Chemistry, 285, 21797–21806.

    PubMed  CAS  Google Scholar 

  • Mutschler, H., Gebhardt, M., Shoeman, R. L., & Meinhart, A. (2011). A novel mechanism of programmed cell death in bacteria by toxin–antitoxin systems corrupts peptidoglycan synthesis. PLoS Biology, 9, e1001033.

    PubMed  CAS  Google Scholar 

  • Nordström, K. (2006). Plasmid R1—replication and its control. Plasmid, 55, 1–26.

    PubMed  Google Scholar 

  • Oberer, M., Lindner, H., Glatter, O., Kratky, C., & Keller, W. (1999). Thermodynamic properties and DNA binding of the ParD protein from the broad host-range plasmid RK2/RP4 killing system. Biological Chemistry, 380, 1413–1420.

    PubMed  CAS  Google Scholar 

  • Oberer, M., Zangger, K., Prytulla, S., & Keller, W. (2002). The anti-toxin ParD of plasmid RK2 consists of two structurally distinct moieties and belongs to the ribbon-helix-helix family of DNA-binding proteins. The Biochemical Journal, 361, 41–47.

    PubMed  CAS  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 Science, 16, 1676–1688.

    PubMed  CAS  Google Scholar 

  • Ogura, T., & Hiraga, S. (1983). Mini-F plasmid genes that couple host cell division to plasmid proliferation. Proceedings of the National Academy of Sciences of the United States of America, 80, 4784–4788.

    PubMed  CAS  Google Scholar 

  • Ortega, S., de Torrontegui, G., & Diaz, R. (1989). Isolation and characterization of a conditional replication mutant of the antibiotic resistance factor R1 affected in the gene of the replication protein repA. Molecular and General Genetics, 217, 111–117.

    PubMed  CAS  Google Scholar 

  • Pachulec, E., & van der Does, C. (2010). Conjugative plasmids of Neisseria gonorrhoeae. PLoS ONE, 5, e9962.

    PubMed  Google Scholar 

  • Pandey, D. P., & Gerdes, K. (2005). Toxin–antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Research, 33, 966–976.

    PubMed  CAS  Google Scholar 

  • Pedersen, K., Zavialov, A. V., Pavlov, M. Y., 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  CAS  Google Scholar 

  • Pimentel, B., Madine, M. A., & de la Cueva-Mendez, G. (2005). Kid cleaves specific mRNAs at UUACU sites to rescue the copy number of plasmid R1. The EMBO Journal, 24, 3459–3469.

    PubMed  CAS  Google Scholar 

  • Potrykus, K., Santos, S., Lemonnier, M., Diaz-Orejas, R., & Wegrzyn, G. (2002) Differential effects of Kid toxin on two modes of replication of lambdoid plasmids suggest that this toxin acts before, but not after, the assembly of the replication complex. Microbiology (Reading, England) 148, 2489–2495.

    Google Scholar 

  • Radnedge, L., Davis, M. A., Youngren, B., & Austin, S. J. (1997). Plasmid maintenance functions of the large virulence plasmid of Shigella flexneri. Journal of Bacteriology, 179, 3670–3675.

    PubMed  CAS  Google Scholar 

  • Rafferty, J. B., Somers, W. S., Saint-Girons, I., & Phillips, S. E. (1989). Three-dimensional crystal structures of Escherichia coli met repressor with and without corepressor. Nature, 341, 705–710.

    PubMed  CAS  Google Scholar 

  • Raumann, B. E., Rould, M. A., Pabo, C. O., & Sauer, R. T. (1994). DNA recognition by beta-sheets in the Arc repressor–operator crystal structure. Nature, 367, 754–757.

    PubMed  CAS  Google Scholar 

  • Rice, L. B., Carias, L. L., Donskey, C. L., & Rudin, S. D. (1998). Transferable, plasmid-mediated vanB-type glycopeptide resistance in Enterococcus faecium. Antimicrobial Agents and Chemotherapy, 42, 963–964.

    PubMed  CAS  Google Scholar 

  • Riise, E., & Molin, S. (1986). Purification and characterization of the CopB replication control protein, and precise mapping of its target site in the R1 plasmid. Plasmid, 15, 163–171.

    PubMed  CAS  Google Scholar 

  • Roberts, R. C., & Helinski, D. R. (1992). Definition of a minimal plasmid stabilization system from the broad-host-range plasmid RK2. Journal of Bacteriology, 174, 8119–8132.

    PubMed  CAS  Google Scholar 

  • Roberts, R. C., Burioni, R., & Helinski, D. R. (1990). Genetic characterization of the stabilizing functions of a region of broad-host-range plasmid RK2. Journal of Bacteriology, 172, 6204–6216.

    PubMed  CAS  Google Scholar 

  • Roberts, R. C., Spangler, C., & Helinski, D. R. (1993). Characteristics and significance of DNA binding activity of plasmid stabilization protein ParD from the broad host-range plasmid RK2. The Journal of Biological Chemistry, 268, 27109–27117.

    PubMed  CAS  Google Scholar 

  • Roberts, R. C., Strom, A. R., & Helinski, D. R. (1994). The parDE operon of the broad-host-range plasmid RK2 specifies growth inhibition associated with plasmid loss. Journal of Molecular Biology, 237, 35–51.

    PubMed  CAS  Google Scholar 

  • Rosvoll, T. C., Pedersen, T., Sletvold, H., Johnsen, P. J., Sollid, J. E., Simonsen, G. S., et al. (2010). PCR-based plasmid typing in Enterococcus faecium strains reveals widely distributed pRE25-, pRUM-, pIP501- and pHTbeta-related replicons associated with glycopeptide resistance and stabilizing toxin–antitoxin systems. FEMS Immunology and Medical Microbiology, 58, 254–268.

    PubMed  CAS  Google Scholar 

  • Ruiz-Echevarria, M. J., Berzal-Herranz, A., Gerdes, K., & Diaz-Orejas, R. (1991a). The kis and kid genes of the parD maintenance system of plasmid R1 form an operon that is autoregulated at the level of transcription by the co-ordinated action of the Kis and Kid proteins. Molecular Microbiology, 5, 2685–2693.

    PubMed  CAS  Google Scholar 

  • Ruiz-Echevarria, M. J., de Torrontegui, G., Gimenez-Gallego, G., & Diaz-Orejas, R. (1991b). Structural and functional comparison between the stability systems ParD of plasmid R1 and Ccd of plasmid F. Molecular and General Genetics, 225, 355–362.

    PubMed  CAS  Google Scholar 

  • Ruiz-Echevarria, M. J., de la Cueva, G., & Diaz-Orejas, R. (1995a). Translational coupling and limited degradation of a polycistronic messenger modulate differential gene expression in the parD stability system of plasmid R1. Molecular and General Genetics, 248, 599–609.

    PubMed  CAS  Google Scholar 

  • Ruiz-Echevarria, M. J., de la Torre, M. A., & Diaz-Orejas, R. (1995b). A mutation that decreases the efficiency of plasmid R1 replication leads to the activation of parD, a killer stability system of the plasmid. FEMS Microbiology Letters, 130, 129–135.

    PubMed  CAS  Google Scholar 

  • Salmon, M. A., Van Melderen, L., Bernard, P., & Couturier, M. (1994). The antidote and autoregulatory functions of the F plasmid CcdA protein: A genetic and biochemical survey. Molecular and General Genetics, 244, 530–538.

    PubMed  CAS  Google Scholar 

  • Santos-Sierra, S., Giraldo, R., & Diaz-Orejas, R. (1997). Functional interactions between homologous conditional killer systems of plasmid and chromosomal origin. FEMS Microbiology Letters, 152, 51–56.

    PubMed  CAS  Google Scholar 

  • Santos-Sierra, S., Pardo-Abarrio, C., Giraldo, R., & Diaz-Orejas, R. (2002). Genetic identification of two functional regions in the antitoxin of the parD killer system of plasmid R1. FEMS Microbiology Letters, 206, 115–119.

    PubMed  CAS  Google Scholar 

  • Simic, M., De Jonge, N., Loris, R., Vesnaver, G., & Lah, J. (2009). Driving forces of gyrase recognition by the addiction toxin CcdB. The Journal of Biological Chemistry, 284, 20002–20010.

    PubMed  CAS  Google Scholar 

  • Sletvold, H., Johnsen, P. J., Hamre, I., Simonsen, G. S., Sundsfjord, A., & Nielsen, K. M. (2008). Complete sequence of Enterococcus faecium pVEF3 and the detection of an omega-epsilon-zeta toxin–antitoxin module and an ABC transporter. Plasmid, 60, 75–85.

    PubMed  CAS  Google Scholar 

  • Smith, A. B., & 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 Research, 34, 4667–4676.

    PubMed  CAS  Google Scholar 

  • Smith, A. S., & Rawlings, D. E. (1997). The poison-antidote stability system of the broad-host-range Thiobacillus ferrooxidans plasmid pTF-FC2. Molecular Microbiology, 26, 961–970.

    PubMed  CAS  Google Scholar 

  • Soberon, N. E., Lioy, V. S., Pratto, F., Volante, A., & Alonso, J. C. (2011). Molecular anatomy of the Streptococcus pyogenes pSM19035 partition and segrosome complexes. Nucleic Acids Research, 39, 2624–2637.

    PubMed  CAS  Google Scholar 

  • Somers, W. S., Rafferty, J. B., Phillips, K., Strathdee, S., He, Y. Y., McNally, T., et al. (1994). The Met repressor–operator complex: DNA recognition by beta-strands. Annals of the New York Academy of Sciences, 726, 105–117.

    PubMed  CAS  Google Scholar 

  • Thomas, C. M., & Helinski, D. R. (1989). Vegetative replication and stable inheritance of IncP plasmids. In C. M. Thomas (Ed.), Promiscuous Plasmids of Gram-Negative Bacteria (pp. 1–25). San Diego: Academic Press.

    Google Scholar 

  • Tian, Q. B., Hayashi, T., Murata, T., & Terawaki, Y. (1996a). Gene product identification and promoter analysis of hig locus of plasmid Rts1. Biochemical and Biophysical Research Communications, 225, 679–684.

    PubMed  CAS  Google Scholar 

  • Tian, Q. B., Ohnishi, M., Tabuchi, A., & Terawaki, Y. (1996b). A new plasmid-encoded proteic killer gene system: Cloning, sequencing, and analyzing hig locus of plasmid Rts1. Biochemical and Biophysical Research Communications, 220, 280–284.

    PubMed  CAS  Google Scholar 

  • Tian, Q. B., Ohnishi, M., Murata, T., Nakayama, K., Terawaki, Y., & Hayashi, T. (2001). Specific protein-DNA and protein–protein interaction in the hig gene system, a plasmid-borne proteic killer gene system of plasmid Rts1. Plasmid, 45, 63–74.

    PubMed  CAS  Google Scholar 

  • Tsuchimoto, S., Ohtsubo, H., & Ohtsubo, E. (1988). Two genes, pemK and pemI, responsible for stable maintenance of resistance plasmid R100. Journal of Bacteriology, 170, 1461–1466.

    PubMed  CAS  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. Journal of Bacteriology, 174, 4205–4211.

    PubMed  CAS  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. Molecular Microbiology, 11, 1151–1157.

    PubMed  Google Scholar 

  • Van Melderen, L., Thi, M. H., Lecchi, P., Gottesman, S., Couturier, M., & Maurizi, M. R. (1996). ATP-dependent degradation of CcdA by Lon protease. Effects of secondary structure and heterologous subunit interactions. The Journal of Biological Chemistry, 271, 27730–27738.

    PubMed  Google Scholar 

  • Yoshizumi, S., Zhang, Y., Yamaguchi, Y., Chen, L., Kreiswirth, B. N., & Inouye, M. (2009). Staphylococcus aureus YoeB homologues inhibit translation initiation. Journal of Bacteriology, 191, 5868–5872.

    PubMed  CAS  Google Scholar 

  • Yuan, J., Sterckx, Y., Mitchenall, L. A., Maxwell, A., Loris, R., & Waldor, M. K. (2010). Vibrio cholerae ParE2 poisons DNA gyrase via a mechanism distinct from other gyrase inhibitors. The Journal of Biological Chemistry, 285, 40397–40408.

    PubMed  CAS  Google Scholar 

  • Zhang, Y., & Inouye, M. (2009). The inhibitory mechanism of protein synthesis by YoeB, an Escherichia coli toxin. The Journal of Biological Chemistry, 284, 6627–6638.

    PubMed  CAS  Google Scholar 

  • Zhang, J., Zhang, Y., Zhu, L., Suzuki, M., & Inouye, M. (2004). Interference of mRNA function by sequence-specific endoribonuclease PemK. The Journal of Biological Chemistry, 279, 20678–20684.

    PubMed  CAS  Google Scholar 

  • Zielenkiewicz, U., & Ceglowski, P. (2005). The toxin–antitoxin system of the streptococcal plasmid pSM19035. Journal of Bacteriology, 187, 6094–6105.

    PubMed  CAS  Google Scholar 

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Acknowledgments

Work in the laboratory was supported by current projects, BFU 2008-01566, CDS2008-0013 (INTERMODS), BFU2011-25939 and by the networks BFU 2008-0079-E/BNC and BFU2011-14145-E. We acknowledge frequent discussions with Juan López-Villarejo and Damian Lobato-Márquez, members of our laboratory. Discussions with Manuel Espinosa and with other members or advisors of the INTERMODS project are also acknowledged.

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  1. Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040, Madrid, Spain

    Elizabeth Diago-Navarro, Ana M. Hernández-Arriaga & Ramón Díaz-Orejas

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  1. Elizabeth Diago-Navarro
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  2. Ana M. Hernández-Arriaga
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  3. Ramón Díaz-Orejas
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Correspondence to Ramón Díaz-Orejas .

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  1. Inst. for Cell and Molecular Bioscience, Centre for Bacterial Cell Biology, Newcastle University, Richardson Road, Newcastle upon Tyne, NE2 4AX, United Kingdom

    Kenn Gerdes

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Diago-Navarro, E., Hernández-Arriaga, A.M., Díaz-Orejas, R. (2013). Type II Toxin-Antitoxin Loci Encoded by Plasmids. In: Gerdes, K. (eds) Prokaryotic Toxin-Antitoxins. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-33253-1_16

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