Biochemistry (Moscow)

, Volume 78, Issue 9, pp 963–970 | Cite as

Bacteria and phenoptosis

  • O. A. KoksharovaEmail author


Genetically programmed death of an organism, or phenoptosis, can be found not only in animals and plants, but also in bacteria. Taking into account intrapopulational relations identified in bacteria, it is easy to imagine the importance of phenoptosis in the regulation of a multicellular bacterial community in the real world of its existence. For example, autolysis of part of the population limits the spread of viral infection. Destruction of cells with damaged DNA contributes to the maintenance of low level of mutations. Phenoptosis can facilitate the exchange of genetic information in a bacterial population as a result of release of DNA from lysed cells. Bacteria use a special “language” to transmit signals in a population; it is used for coordinated regulation of gene expression. This special type of regulation of bacterial gene expression is usually active at high densities of bacteria populations, and it was named “quorum sensing” (QS). Different molecules can be used for signaling purposes. Phenoptosis, which is carried out by toxin-antitoxin systems, was found to depend on the density of the population; it requires a QS factor, which is called the extracellular death factor. The study of phenoptosis in bacteria is of great practical importance. The components that make up the systems ensuring the programmed cell death, including QS factor, may be used for the development of drugs that will activate mechanisms of phenoptosis and promote the destruction of pathogenic bacteria. Comparative genomic analysis revealed that the genes encoding several key enzymes involved in apoptosis of eukaryotes, such as paracaspases and metacaspases, apoptotic ATPases, proteins containing NACHT leucine-rich repeat, and proteases similar to mitochondrial HtrA-like protease, have homologs in bacteria. Proteomics techniques have allowed for the first time to identify the proteins formed during phenoptosis that participate in orderly liquidation of Streptomyces coelicolor and Escherichia coli cells. Among these proteins enzymes have been found that are involved in the degradation of cellular macromolecules, regulatory proteins, and stress-induced proteins. Future studies involving methods of biochemistry, genetics, genomics, proteomics, transcriptomics, and metabolomics should support a better understanding of the “mystery” of bacterial programmed cell death; this knowledge might be used to control bacterial populations.

Key words

bacteria phenoptosis programmed cell death cell population QS autoinducers extracellular death factor comparative genomics proteomics 



apoptotic-like death


extracellular death factor


programmed cell death


quorum sensing

TA complex

toxin-antitoxin complex


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  1. 1.
    Skulachev, V. P. (1997) Biochemistry (Moscow), 62, 1191–1195.Google Scholar
  2. 2.
    Skulachev, V. P. (1999) Biochemistry (Moscow), 64, 1418–1426.Google Scholar
  3. 3.
    Longo, V. D., Mitteldorf, J., and Skulachev, V. P. (2005) Nat. Rev. Genet., 6, 886–872.CrossRefGoogle Scholar
  4. 4.
    Skulachev, V. P. (2012) Biochemistry (Moscow), 77, 689–706.CrossRefGoogle Scholar
  5. 5.
    Oleskin, A. V. (2001) Soros Obrazovat. Zh., 8, 7–12.Google Scholar
  6. 6.
    Gordeeva, A. V., Labas, Y. A., and Zvyagilskaya, R. A. (2004) Biochemistry (Moscow), 69, 1055–1066.CrossRefGoogle Scholar
  7. 7.
    Prozorov, A. A., and Danilenko, V. N. (2010) Microbiology (Moscow), 79, 129–140.CrossRefGoogle Scholar
  8. 8.
    Lee, H. H., Molla, M. N., Cantor, C. R., and Collins, J. J. (2010) Nature, 467, 82–85.PubMedCrossRefGoogle Scholar
  9. 9.
    Tanouchi, Y., Pai, A., Buchler, N. E., and You, L. (2012) Mol. Syst. Biol., 8, 626.PubMedCrossRefGoogle Scholar
  10. 10.
    Reuven, P., and Avigdor, E. (2011) Curr. Opin. Genet. Dev., 21, 759–767.PubMedCrossRefGoogle Scholar
  11. 11.
    Khmel, I. A. (2006) Microbiology (Moscow), 75, 390–397.CrossRefGoogle Scholar
  12. 12.
    Khmel, I. A., and Metlitskaya, A. Z. (2006) Mol. Biol. (Moscow), 40, 169–182.CrossRefGoogle Scholar
  13. 13.
    Waters, C., and Bassler, B. (2005) Annu. Rev. Cell Dev. Biol., 21, 319–346.PubMedCrossRefGoogle Scholar
  14. 14.
    Miller, M. B., and Bassler, B. L. (2001) Annu. Rev. Microbiol., 55, 165–199.PubMedCrossRefGoogle Scholar
  15. 15.
    Shpakov, A. O. (2009) Microbiology (Moscow), 78, 133–143.CrossRefGoogle Scholar
  16. 16.
    Carmona-Fontaine, C., and Xavier, J. B. (2012) Mol. Syst. Biol., 8, 627–628.PubMedCrossRefGoogle Scholar
  17. 17.
    Mittenhuber, G. (1999) J. Mol. Microbiol. Biotechnol., 1, 295–302.PubMedGoogle Scholar
  18. 18.
    Hayes, F. (2003) Science, 301, 1496–1499.PubMedCrossRefGoogle Scholar
  19. 19.
    Pandey, D. P., and Gerdes, K. (2005) Nucleic Acids Res., 33, 966–976.PubMedCrossRefGoogle Scholar
  20. 20.
    Gerdes, K., and Wagner, E. G. (2007) Curr. Opin. Microbiol., 10, 117–124.PubMedCrossRefGoogle Scholar
  21. 21.
    Fozo, E. M., Hemm, M. R., and Storz, G. (2008) Microbiol. Mol. Biol. Rev., 72, 579–589.PubMedCrossRefGoogle Scholar
  22. 22.
    Fineran, P. C., Blower, T. R., Foulds, I. J., Humphreys, D. P., Lilley, K. S., and Salmond, G. P. (2009) Proc. Natl. Acad. Sci. USA, 106, 894–899.PubMedCrossRefGoogle Scholar
  23. 23.
    Gerdes, K., Christensen, S. K., and Lobner-Olesen, A. (2005) Nat. Rev. Microbiol., 3, 371–382.PubMedCrossRefGoogle Scholar
  24. 24.
    Yamaguchi, Y., Park, J. H., and Inouye, M. (2011) Annu. Rev. Genet., 45, 61–79.PubMedCrossRefGoogle Scholar
  25. 25.
    Mutschler, H., Gebhardt, M., Shoeman, R. L., and Meinhart, A. (2011) PLoS Biol., 9, e1001033.PubMedCrossRefGoogle Scholar
  26. 26.
    Aizenman, E., Engelberg-Kulka, H., and Glaser, G. (1996) Proc. Natl. Acad. Sci. USA, 93, 6059–6063.PubMedCrossRefGoogle Scholar
  27. 27.
    Mittenhuber, G. (1999) J. Mol. Microbiol. Biotechnol., 1, 295–302.PubMedGoogle Scholar
  28. 28.
    Engelberg-Kulka, H., Hazan, R., and Amitai, S. (2005) J. Cell Sci., 118, 4327–4332.PubMedCrossRefGoogle Scholar
  29. 29.
    Zhang, Y., Zhang, J., Hoeflich, K. P., Ikura, M., Qing, G., and Inouye, M. (2003) Mol. Cell, 12, 913–923.PubMedCrossRefGoogle Scholar
  30. 30.
    Zhang, Y., Zhang, J., Hara, H., Kato, I., and Inouye, M. (2005) J. Biol. Chem., 280, 3143–3150.PubMedCrossRefGoogle Scholar
  31. 31.
    Hazan, R., Sat, B., and Engelberg-Kulka, H. (2004) J. Bacteriol., 186, 3663–3669.PubMedCrossRefGoogle Scholar
  32. 32.
    Hayes, F. (2003) Science, 301, 1496–1499.PubMedCrossRefGoogle Scholar
  33. 33.
    Gerdes, K., Christensen, S. K., and Lobner-Olesen, A. (2005) Nat. Rev. Microbiol., 3, 371–382.PubMedCrossRefGoogle Scholar
  34. 34.
    Pandey, D. P., and Gerdes, K. (2005) Nucleic Acids Res., 33, 966–976.PubMedCrossRefGoogle Scholar
  35. 35.
    Makarova, K., Wolf, Y., and Koonin, E. (2009) Biol. Direct., 4, 19.PubMedCrossRefGoogle Scholar
  36. 36.
    Leplae, R., Geeraerts, D., Hallez, R., Guglielmini, J., Dreze, P., and van Melderen, L. (2011) Nucleic Acids Res., 39, 5513–5525.PubMedCrossRefGoogle Scholar
  37. 37.
    Yamaguchi, Y., and Inouye, M. (2011) Nat. Rev. Microbiol., 9, 779–790.PubMedCrossRefGoogle Scholar
  38. 38.
    Maisonneuve, E., Shakespeare, L. J., Jorgensen, M. G., and Gerdes, K. (2011) Proc. Natl. Acad. Sci. USA, 108, 13206–13211.PubMedCrossRefGoogle Scholar
  39. 39.
    Kolodkin-Gal, I., Hazan, R., Gaathon, A., Carmeli, S., and Engelberg-Kulka, H. (2007) Science, 318, 652–655.PubMedCrossRefGoogle Scholar
  40. 40.
    Kolodkin-Gal, I., and Engelberg-Kulka, H. (2008) J. Bacteriol., 190, 3169–3175.PubMedCrossRefGoogle Scholar
  41. 41.
    Amitai, S., Kolodkin-Gal, I., Hananya-Meltabashi, M., Sacher, A., and Engelberg-Kulka, H. (2009) PLoS Genet., 5, e1000390; doi: 10.1371/journal.pgen.1000390.Google Scholar
  42. 42.
    Belitsky, M., Avshalom, H., Erental, A., Yelin, I., Kumar, S., London, N., Sperber, M., Schueler-Furman, O., and Engelberg-Kulka, H. (2011) Mol. Cell, 41, 625–635.PubMedCrossRefGoogle Scholar
  43. 43.
    Zhang, Y., Zhu, L., Zhang, J., and Inouye, M. (2005) J. Biol. Chem., 280, 26080–26088.PubMedCrossRefGoogle Scholar
  44. 44.
    Erental, A., Sharon, I., and Engelberg-Kulka, H. (2012) PLoS Biol., 10, e1001281; doi: 10.1371/journal.pbio.1001281.Google Scholar
  45. 45.
    Engelberg-Kulka, H., Sat, B., Reches, M., Amitai, S., and Hazan, R. (2004) Trends Microbiol., 12, 66–71.PubMedCrossRefGoogle Scholar
  46. 46.
    Koonin, E. V., and Aravind, L. (2002) Cell Death Differ., 9, 394–404.PubMedCrossRefGoogle Scholar
  47. 47.
    Frade, J. M., and Michaelidis, T. M. (1997) Bioessays, 19, 827–832.PubMedCrossRefGoogle Scholar
  48. 48.
    Koksharova, O. A. (2010) Microbiology, 79, 721–734.CrossRefGoogle Scholar
  49. 49.
    Bidle, K. D., and Falkowski, P. G. (2004) Nat. Rev. Microbiol., 2, 643–655.PubMedCrossRefGoogle Scholar
  50. 50.
    Berman-Frank, I., Bidle, K., Haramaty, L., and Falkowski, P. (2004) Limnol. Oceanogr., 49, 997–1005.CrossRefGoogle Scholar
  51. 51.
    Moharikar, S., D’Souza, J. S., Kulkarni, A. B., and Rao, B. J. (2006) J. Phycol., 42, 423–433.CrossRefGoogle Scholar
  52. 52.
    Segovia, M., Haramaty, L., Berges, J. A., and Falkowski, P. G. (2003) Plant Physiol., 132, 99–105.PubMedCrossRefGoogle Scholar
  53. 53.
    Vardi, A., Berman-Frank, I., Rozenberg, T., Hadas, O., Kaplan, A., and Levine, A. (1999) Curr. Biol., 9, 1061–1064.PubMedCrossRefGoogle Scholar
  54. 54.
    Thornberry, N. A., and Lazebnik, Y. (1998) Science, 281, 1312–1316.PubMedCrossRefGoogle Scholar
  55. 55.
    Uren, A. G., O’Rourke, K., Pisabarro, M. T., Seshagiri, S., Koonin, E. V., and Dixit, V. M. (2000) Mol. Cell, 6, 961–967.PubMedGoogle Scholar
  56. 56.
    Madeo, F., Herker, E., Maldener, C., Wissing, S., Lachelt, S., Herlan, M., Fehr, M., Lauber, K., Sigrist, S. J., Wesselborg, S., and Frohlich, K.-U. (2002) Mol. Cell, 9, 911–917.PubMedCrossRefGoogle Scholar
  57. 57.
    Szallies, A., Kubata, B. K., and Duszenko, M. (2002) FEBS Lett., 517, 144–150.PubMedCrossRefGoogle Scholar
  58. 58.
    Kusters, J. G., Gerrits, M. M., van Strijp, J. A., and Vandenbroucke-Grauls, C. M. (1997) Infect. Immun., 65, 3672–3679.PubMedGoogle Scholar
  59. 59.
    Ning, S. B., Guo, H. L., Wang, L., and Song, Y. C. (2002) J. Appl. Microbiol., 93, 15–28.PubMedCrossRefGoogle Scholar
  60. 60.
    Gautam, S., and Sharma, A. (2002) Mol. Microbiol., 44, 393–401.PubMedCrossRefGoogle Scholar
  61. 61.
    Bayles, K. W. (2003) Trends Microbiol., 11, 306–311.PubMedCrossRefGoogle Scholar
  62. 62.
    Manteca, A., Fernandez, M., and Sanchez, J. (2006) Res. Microbiol., 157, 143–152.PubMedCrossRefGoogle Scholar
  63. 63.
    Leipe, D. D., Koonin, E. V., and Aravind, L. (2004) J. Mol. Biol., 343, 1–28.PubMedCrossRefGoogle Scholar
  64. 64.
    Manteca, A., Mader, U., Connolly, B. A., and Sanchez, J. (2006) Proteomics, 6, 6008–6022.PubMedCrossRefGoogle Scholar
  65. 65.
    He, Y. W., and Zhang, L. H. (2008) FEMS Microbiol. Rev., 32, 842–857.PubMedCrossRefGoogle Scholar
  66. 66.
    Tao, F., He, Y. W., Wu, D. H., Swarup, S., and Zhang, L. H. (2010) J. Bacteriol., 192, 1020–1029.PubMedCrossRefGoogle Scholar
  67. 67.
    Amitai, S., Kolodkin-Gal, I., Hananya-Meltabashi, M., Sacher, A., and Engelberg-Kulka, H. (2009) PLoS Genet., 5, e1000390.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2013

Authors and Affiliations

  1. 1.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Institute of Molecular GeneticsRussian Academy of SciencesMoscowRussia

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