Advertisement

Type III Toxin-Antitoxin Loci

  • Tim R. Blower
  • Francesca L. Short
  • George P. C. Salmond
Chapter

Abstract

The toxIN locus from a cryptic plasmid of the plant pathogen Pectobacterium atrosepticum was the first type III toxin–antitoxin (TA) system to be identified. This new paradigm describes how an RNA antitoxin directly interacts with and inhibits a protein toxin. Within this chapter, we discuss the discovery of toxIN as a potent bacteriophage resistance mechanism and the subsequent genetic, biochemical and structural studies that allowed construction of generalised working models for the activities of these novel systems. Furthermore, the recent identification of three independent families of type III systems, suggests the possibility of wider biological roles. Although type III TA loci had perhaps been initially considered a niche field, it is now clear that these systems are widespread, and thus presumably important in the biology of prokaryotes.

Keywords

Phage Infection Cryptic Plasmid Phage Resistance Abortive Infection Host Background 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Funding is provided by the Biotechnology and Biological Sciences Research Council (UK), and the Department for Business, Innovation and Skills (UK) together with the Cambridge Commonwealth Trust (UK).

References

  1. Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990). Basic local alignment search tool. Journal of Molecular Biology, 215, 403–410.PubMedGoogle Scholar
  2. Bell, K. S., Sebaihia, M., Pritchard, L., Holden, M. T., Hyman, L. J., Holeva, M. C., et al. (2004). Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors. Proceedings of the National Academy of Sciences of the United States of America, 101, 11105–11110.PubMedCrossRefGoogle Scholar
  3. Bidnenko, E., Chopin, A., Ehrlich, S. D., & Chopin, M. C. (2009). Activation of mRNA translation by phage protein and low temperature: The case of Lactococcus lactis abortive infection system AbiD1. BMC Molecular Biology, 10, 4.PubMedCrossRefGoogle Scholar
  4. Blower, T. R., Fineran, P. C., Johnson, M. J., Toth, I. K., Humphreys, D. P., & Salmond, G. P. (2009). Mutagenesis and functional characterisation of the RNA and protein components of the toxIN abortive infection and toxin–antitoxin locus of Erwinia. Journal of Bacteriology, 191, 6029–6039.PubMedCrossRefGoogle Scholar
  5. Blower, T. R., Pei, X. Y., Short, F. L., Fineran, P. C., Humphreys, D. P., Luisi, B. F., et al. (2011a). A processed non-coding RNA regulates an altruistic bacterial antiviral system. Nature Structural and Molecular Biology, 18, 185–190.PubMedCrossRefGoogle Scholar
  6. Blower, T. R., Salmond, G. P., & Luisi, B. F. (2011b). Balancing at survival’s edge: The structure and adaptive benefits of prokaryotic toxin–antitoxin partners. Current Opinion in Structural Biology, 21, 109–118.PubMedCrossRefGoogle Scholar
  7. Blower, T. R., Short, F. L., Rao, F., Mizuguchi, K., Pei, X. Y., Fineran, P. C., Luisi, B. F., & Salmond, G. P. (2012). Identification and classification of bacterial Type III toxin–antitoxin systems encoded in chromosomal and plasmid genomes. Nucleic Acids Research. doi: 10.1093/nar/gks231.
  8. Chakrabarti, P., & Janin, J. (2002). Dissecting protein–protein recognition sites. Proteins, 47, 334–343.PubMedCrossRefGoogle Scholar
  9. Chibani-Chennoufi, S., Bruttin, A., Dillmann, M. L., & Brussow, H. (2004). Phage-host interaction: An ecological perspective. Journal of Bacteriology, 186, 3677–3686.PubMedCrossRefGoogle Scholar
  10. Chopin, M. C., Chopin, A., & Bidnenko, E. (2005). Phage abortive infection in lactococci: Variations on a theme. Current Opinion in Microbiology, 8, 473–479.PubMedCrossRefGoogle Scholar
  11. Chowdhury, R., Biswas, S. K., & Das, J. (1989). Abortive replication of choleraphage Φ149 in Vibrio cholerae biotype el tor. Journal of Virology, 63, 392–397.PubMedGoogle Scholar
  12. Emond, E., Dion, E., Walker, S. A., Vedamuthu, E. R., Kondo, J. K., & Moineau, S. (1998). AbiQ, an abortive infection mechanism from Lactococcus lactis. Applied and Environment Microbiology, 64, 4748–4756.Google Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. Forde, A., & Fitzgerald, G. F. (1999). Bacteriophage defence systems in lactic acid bacteria. Antonie van Leeuwenhoek, 76, 89–113.PubMedCrossRefGoogle Scholar
  15. Fuhrman, J. A. (1999). Marine viruses and their biogeochemical and ecological effects. Nature, 399, 541–548.PubMedCrossRefGoogle Scholar
  16. Guzman, L. M., Belin, D., Carson, M. J., & Beckwith, J. (1995). Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. Journal of Bacteriology, 177, 4121–4130.PubMedGoogle Scholar
  17. Haaber, J., Samson, J. E., Labrie, S. J., Campanacci, V., Cambillau, C., Moineau, S., et al. (2010). Lactococcal abortive infection protein AbiV interacts directly with the phage protein SaV and prevents translation of phage proteins. Applied and Environment Microbiology, 76, 7085–7092.CrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. Hazan, R., & Engelberg-Kulka, H. (2004). Escherichia coli mazEF-mediated cell death as a defense mechanism that inhibits the spread of phage P1. Molecular Genetics and Genomics, 272, 227–234.PubMedCrossRefGoogle Scholar
  20. Hill, C. (1993). Bacteriophage and bacteriophage resistance in lactic acid bacteria. FEMS Microbiology Reviews, 12, 87–108.CrossRefGoogle Scholar
  21. Holm, L., & Sander, C. (1993). Protein structure comparison by alignment of distance matrices. Journal of Molecular Biology, 233, 123–138.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. Klein, D. J., Edwards, T. E., & Ferre-D’Amare, A. R. (2009). Cocrystal structure of a class I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase. Nature Structural and Molecular Biology, 16, 343–344.PubMedCrossRefGoogle Scholar
  24. Kutter, E., & Sulakvelidze, A. (2005). Bacteriophages: Biology and applications. Boca Raton, Florida, USA: CRC Press.Google Scholar
  25. Labrie, S. J., Samson, J. E., & Moineau, S. (2010). Bacteriophage resistance mechanisms. Nature Reviews Microbiology, 8, 317–327.PubMedCrossRefGoogle Scholar
  26. Lima-Mendez, G., Toussaint, A., & Leplae, R. (2007). Analysis of the phage sequence space: The benefit of structured information. Virology, 365, 241–249.PubMedCrossRefGoogle Scholar
  27. Magnuson, R. D. (2007). Hypothetical functions of toxin–antitoxin systems. Journal of Bacteriology, 189, 6089–6092.PubMedCrossRefGoogle Scholar
  28. McGrath, S., & van Sinderen, D. (2007). Bacteriophage genetics and molecular biology. Norfolk: Caister Academic Press.Google Scholar
  29. Nissen, P., Ippolito, J. A., Ban, N., Moore, P. B., & Steitz, T. A. (2001). RNA tertiary interactions in the large ribosomal subunit: The A-minor motif. Proceedings of the National Academy of Sciences of the United States of America, 98, 4899–4903.PubMedCrossRefGoogle Scholar
  30. Otsuka, Y., & Yonesaki, T. (2012). Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins. Molecular Microbiology, 83, 669–681.PubMedCrossRefGoogle Scholar
  31. Pecota, D. C., & Wood, T. K. (1996). Exclusion of T4 phage by the hok/sok killer locus from plasmid R1. Journal of Bacteriology, 178, 2044–2050.PubMedGoogle Scholar
  32. Puglisi, J. D., Wyatt, J. R., & Tinoco, I, Jr. (1988). A pseudoknotted RNA oligonucleotide. Nature, 331, 283–286.PubMedCrossRefGoogle Scholar
  33. Scaltriti, E., Moineau, S., Launay, H., Masson, J. Y., Rivetti, C., Ramoni, R., et al. (2010). Deciphering the function of lactococcal phage ul36 Sak domains. Journal of Structural Biology, 170, 462–469.PubMedCrossRefGoogle Scholar
  34. Scaltriti, E., Launay, H., Genois, M. M., Bron, P., Rivetti, C., Grolli, S., et al. (2011). Lactococcal phage p2 ORF35-Sak3 is an ATPase involved in DNA recombination and AbiK mechanism. Molecular Microbiology, 80, 102–116.PubMedCrossRefGoogle Scholar
  35. Shi, J., Blundell, T. L., & Mizuguchi, K. (2001). FUGUE: Sequence-structure homology recognition using environment-specific substitution tables and structure-dependent gap penalties. Journal of Molecular Biology, 310, 243–257.PubMedCrossRefGoogle Scholar
  36. Shub, D. A. (1994). Bacterial viruses. Bacterial altruism? Current Biology, 4, 555–556.PubMedCrossRefGoogle Scholar
  37. Smith, H. S., Pizer, L. I., Pylkas, L., & Lederberg, S. (1969). Abortive infection of Shigella dysenteriae P2 by T2 bacteriophage. Journal of Virology, 4, 162–168.PubMedGoogle Scholar
  38. Snyder, L. (1995). Phage-exclusion enzymes: A bonanza of biochemical and cell biology reagents? Molecular Microbiology, 15, 415–420.PubMedCrossRefGoogle Scholar
  39. Sorek, R., Kunin, V., & Hugenholtz, P. (2008). CRISPR–a widespread system that provides acquired resistance against phages in bacteria and archaea. Nature Reviews Microbiology, 6, 181–186.PubMedCrossRefGoogle Scholar
  40. Sussman, D., Nix, J. C., & Wilson, C. (2000). The structural basis for molecular recognition by the vitamin B12 RNA aptamer. Natural Structural Biology, 7, 53–57.CrossRefGoogle Scholar
  41. Whitman, W. B., Coleman, D. C., & Wiebe, W. J. (1998). Prokaryotes: The unseen majority. Proceedings of the National Academy of Sciences of the United States of America, 95, 6578–6583.PubMedCrossRefGoogle Scholar
  42. Wimberly, B. T., Brodersen, D. E., Clemons, W. M, Jr, Morgan-Warren, R. J., Carter, A. P., Vonrhein, C., et al. (2000). Structure of the 30S ribosomal subunit. Nature, 407, 327–339.PubMedCrossRefGoogle Scholar
  43. Wommack, K. E., & Colwell, R. R. (2000). Virioplankton: Viruses in aquatic ecosystems. Microbiology and Molecular Biology Reviews, 64, 69–114.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Tim R. Blower
    • 1
  • Francesca L. Short
    • 1
  • George P. C. Salmond
    • 1
  1. 1.Department of BiochemistryUniversity of CambridgeCambridgeUK

Personalised recommendations