БИОХИМИЯ, 2021, том 86, вып. 4, с. 529–553

УДК 577.2

Микробный арсенал противовирусной защиты. Глава II

Обзор

© 2021 А.Б. Исаев 1*, О.С. Мушарова 1,2, К.В. Северинов 1,3*

Сколковский институт науки и технологий, 143028 Москва, Россия; электронная почта: tcft18@gmail.com

Институт молекулярной генетики РАН, 119334 Москва, Россия

Waksman Institute of Microbiology, Piscataway, NJ 08854, USA; e-mail: severik@waksman.rutgers.edu

Поступила в редакцию 30.08.2020
После доработки 29.01.2021
Принята к публикации 29.01.2021

DOI: 10.31857/S0320972521040060

КЛЮЧЕВЫЕ СЛОВА: бактериофаги, иммунные системы, CRISPR-Cas, абортивная инфекция, токсин-антитоксин, PICI, прокариотический белок Argonaute, CBASS.

Статья на английском языке опубликована в режиме Open Access (открытого доступа) на сайте издательства Springer. DOI: 10.1134/S0006297921040064.

Аннотация

Бактериофаги, или фаги, представляют собой вирусы, которые инфицируют бактериальные клетки (в рамках этого обзора мы также рассмотрим вирусы, которые инфицируют архей). Постоянная угроза заражения фагами является одной из основных движущих сил эволюции бактериальных геномов. Чтобы противостоять инфекции, бактерии выработали многочисленные защитные стратегии, позволяющие избежать распознавания фагами или прямо препятствующие размножению фагов внутри клетки. Исследования бактериофагов и бактериальных систем защиты были исторически тесно переплетены с развитием методов классической молекулярной биологии и генной инженерии. В настоящее время благодаря распространению фаговой терапии, широкому применению технологий CRISPR-Cas и развитию биоинформатических подходов, которые облегчают задачу обнаружения новых систем, исследования в области биологии фагов переживают возрождение. В настоящем обзоре описываются различные стратегии, используемые микробами для того, чтобы противостоять фаговой инфекции. Вторая глава посвящена системам адаптивного иммунитета, механизмам абортивной инфекции, защитным системам, связанным с мобильными генетическими элементами, и новым системам, которые были открыты в последние годы с помощью метагеномного майнинга.

Сноски

* Адресат для корреспонденции.

Финансирование

Выполнение данной работы проходило при поддержке Российского фонда фундаментальных исследований (грант № 19-14-50560). АИ поддержан грантом Российского фонда фундаментальных исследований (№ 19-34-90160), OM поддержана грантом Российского научного фонда (№ 19-74-00118). Оплата открытого доступа английской версии статьи: Сколковский Институт Науки и Технологий.

Благодарности

Авторы выражают благодарность Андрею Кульбачинскому за критическое прочтение раздела, посвящённого белку pAgo.

Вклад авторов

ОМ и АИ написали раздел CRISPR-Cas, АИ подготовил остальную часть статьи, АИ и ОМ подготовили рисунки, КС отредактировал текст.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит каких-либо исследований с участием людей или использованием животных в качестве объектов.

Список литературы

1. Jansen, R., Embden, J. D. A., van Gaastra, W., and Schouls, L. M. (2002) Identification of genes that are associated with DNA repeats in prokaryotes, Mol. Microbiol., 43, 1565-1575.

2. Mojica, F. J. M., and Garrett, R. A. (2013) Discovery and seminal developments in the CRISPR field, In CRISPR-Cas Systems, Springer, pp. 1-31.

3. Nussenzweig, P. M., and Marraffini, L. A. (2020) Molecular mechanisms of CRISPR-Cas immunity in bacteria, Annu. Rev. Genet., 54, 93-120.

4. Makarova, K. S., Wolf, Y. I., Iranzo, J., Shmakov, S. A., Alkhnbashi, O. S., et al. (2020) Evolutionary classification of CRISPR-Cas systems: a burst of class 2 and derived variants, Nat. Rev. Microbiol., 18, 67-83.

5. Jackson, R. N., and Wiedenheft, B. (2015) A conserved structural chassis for mounting versatile CRISPR RNA-guided immune responses, Mol. Cell, 58, 722-728.

6. Liu, T. Y., and Doudna, J. A. (2020) Chemistry of Class 1 CRISPR-Cas effectors: binding, editing, and regulation, J. Biol. Chem., 295, 14473-14487.

7. Reeks, J., Graham, S., Anderson, L., Liu, H., White, M. F., and Naismith, J. H. (2013) Structure of the archaeal Cascade subunit Csa5: relating the small subunits of CRISPR effector complexes, RNA Biol., 10, 762-769.

8. Jore, M. M., Lundgren, M., van Duijn, E., Bultema, J. B., Westra, E. R., et al. (2011) Structural basis for CRISPR RNA-guided DNA recognition by Cascade, Nat. Struct. Mol. Biol., 18, 529-536.

9. Wiedenheft, B., Lander, G. C., Zhou, K., Jore, M. M., Brouns, S.J. J., et al. (2011) Structures of the RNA-guided surveillance complex from a bacterial immune system, Nature, 477, 486-489.

10. Sinkunas, T., Gasiunas, G., Waghmare, S. P., Dickman, M. J., Barrangou, R., et al. (2013) In vitro reconstitution of Cascade-mediated CRISPR immunity in Streptococcus thermophilus, EMBO J., 32, 385-394.

11. Benda, C., Ebert, J., Scheltema, R. A., Schiller, H. B., Baumgärtner, M., et al. (2014) Structural model of a CRISPR RNA-silencing complex reveals the RNA-target cleavage activity in Cmr4, Mol. Cell, 56, 43-54.

12. Rouillon, C., Zhou, M., Zhang, J., Politis, A., Beilsten-Edmands, V., et al. (2013) Structure of the CRISPR interference complex CSM reveals key similarities with cascade, Mol. Cell, 52, 124-134.

13. Hale, C. R., Zhao, P., Olson, S., Duff, M. O., Graveley, B. R., Wells, L., et al. (2009) RNA-guided RNA cleavage by a CRISPR RNA–Cas protein complex, Cell, 139, 945-956.

14. Zhang, J., Kasciukovic, T., and White, M. F. (2012) The CRISPR associated protein Cas4 Is a 5′ to 3′ DNA exonuclease with an iron-sulfur cluster, PLoS One, 7, e47232.

15. Elmore, J. R., Sheppard, N. F., Ramia, N., Deighan, T., Li, H., et al. (2016) Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR-Cas system, Genes Dev., 30, 447-459.

16. Estrella, M. A., Kuo, F.-T., and Bailey, S. (2016) RNA-activated DNA cleavage by the type III-B CRISPR-Cas effector complex, Genes Dev., 30, 460-470.

17. Kazlauskiene, M., Tamulaitis, G., Kostiuk, G., Venclovas, Č., and Siksnys, V. (2016) Spatiotemporal control of type III-A CRISPR-Cas immunity: coupling DNA degradation with the target RNA recognition, Mol. Cell, 62, 295-306.

18. Samai, P., Pyenson, N., Jiang, W., Goldberg, G. W., Hatoum-Aslan, A., and Marraffini, L. A. (2015) Co-transcriptional DNA and RNA cleavage during type III CRISPR-Cas immunity, Cell, 161, 1164-1174.

19. Liu, T., Pan, S., Li, Y., Peng, N., and She, Q. (2017) Type III CRISPR-Cas system: introduction and its application for genetic manipulations, Curr. Issues Mol. Biol., 26,1-14.

20. Goldberg, G. W., Jiang, W., Bikard, D., and Marraffini, L. A. (2014) Conditional tolerance of temperate phages via transcription-dependent CRISPR-Cas targeting, Nature, 514, 633-637.

21. Kazlauskiene, M., Kostiuk, G., Venclovas, Č., Tamulaitis, G., and Siksnys, V. (2017) A cyclic oligonucleotide signaling pathway in type III CRISPR-Cas systems, Science, 357, 605-609.

22. Niewoehner, O., Garcia-Doval, C., Rostøl, J. T., Berk, C., Schwede, F., et al. (2017) Type III CRISPR-Cas systems produce cyclic oligoadenylate second messengers, Nature, 548, 543-548.

23. You, L., Ma, J., Wang, J., Artamonova, D., Wang, M., et al. (2019) Structure studies of the CRISPR-Csm complex reveal mechanism of co-transcriptional interference, Cell, 176, 239-253.

24. Koonin, E. V, and Makarova, K. S. (2017) Mobile genetic elements and evolution of CRISPR-Cas systems: all the way there and back, Genome Biol. Evol., 9, 2812-2825.

25. Özcan, A., Pausch, P., Linden, A., Wulf, A., Schühle, K., et al. (2019) Type IV CRISPR RNA processing and effector complex formation in Aromatoleum aromaticum, Nat. Microbiol., 4, 89-96.

26. Makarova, K. S., Wolf, Y. I., Alkhnbashi, O. S., Costa, F., Shah, S. A., et al. (2015) An updated evolutionary classification of CRISPR-Cas systems, Nat. Rev. Microbiol., 13, 722-736.

27. Koonin, E. V, and Makarova, K. S. (2019) Origins and evolution of CRISPR-Cas systems, Philos. Trans. R. Soc. B, 374, 20180087.

28. Pinilla-Redondo, R., Mayo-Muñoz, D., Russel, J., Garrett, R. A., Randau, L., et al. (2020) Type IV CRISPR-Cas systems are highly diverse and involved in competition between plasmids, Nucleic Acids Res., 48, 2000-2012.

29. Gasiunas, G., Barrangou, R., Horvath, P., and Siksnys, V. (2012) Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria, Proc. Natl. Acad. Sci. USA, 109, E2579-E2586.

30. Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J. A., and Charpentier, E. (2012) A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity, Science, 337, 816-821.

31. Hsu, P. D., Lander, E. S., and Zhang, F. (2014) Development and applications of CRISPR-Cas9 for genome engineering, Cell, 157, 1262-1278.

32. Mali, P., Esvelt, K. M., and Church, G. M. (2013) Cas9 as a versatile tool for engineering biology, Nat. Methods, 10, 957-963.

33. Sander, J. D., and Joung, J. K. (2014) CRISPR-Cas systems for editing, regulating and targeting genomes, Nat. Biotechnol., 32, 347-355.

34. Zetsche, B., Gootenberg, J. S., Abudayyeh, O. O., Slaymaker, I. M., Makarova, K. S., et al. (2015) Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system, Cell, 163, 759-771.

35. Yamano, T., Zetsche, B., Ishitani, R., Zhang, F., Nishimasu, H., and Nureki, O. (2017) Structural basis for the canonical and non-canonical PAM recognition by CRISPR-Cpf1, Mol. Cell, 67, 633-645.

36. Chen, J. S., Ma, E., Harrington, L. B., Da Costa, M., Tian, X., et al. (2018) CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity, Science, 360, 436-439.

37. Harrington, L. B., Burstein, D., Chen, J. S., Paez-Espino, D., Ma, E., et al. (2018) Programmed DNA destruction by miniature CRISPR-Cas14 enzymes, Science, 362, 839-842.

38. Chylinski, K., Makarova, K. S., Charpentier, E., and Koonin, E. V (2014) Classification and evolution of type II CRISPR-Cas systems, Nucleic Acids Res., 42, 6091-6105.

39. Shmakov, S., Abudayyeh, O. O., Makarova, K. S., Wolf, Y. I., Gootenberg, J. S., et al. (2015) Discovery and functional characterization of diverse class 2 CRISPR-Cas systems, Mol. Cell, 60, 385-397.

40. Abudayyeh, O. O., Gootenberg, J. S., Konermann, S., Joung, J., Slaymaker, I. M., et al. (2016) C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector, Science, 353, aaf5573, doi: 10.1126/science.aaf5573.

41. Koonin, E. V, and Krupovic, M. (2015) Evolution of adaptive immunity from transposable elements combined with innate immune systems, Nat. Rev. Genet., 16, 184-192.

42. Koonin, E. V, Makarova, K. S., and Zhang, F. (2017) Diversity, classification and evolution of CRISPR-Cas systems, Curr. Opin. Microbiol., 37, 67-78.

43. Makarova, K. S., and Koonin, E. V (2013) Evolution and classification of CRISPR-Cas systems and cas protein families, in CRISPR-Cas System, Springer, pp. 61-91.

44. Nuñez, J. K., Kranzusch, P. J., Noeske, J., Wright, A. V., Davies, C. W., and Doudna, J. A. (2014) Cas1–Cas2 complex formation mediates spacer acquisition during CRISPR-Cas adaptive immunity, Nat. Struct. Mol. Biol., 21, 528.

45. Nuñez, J. K., Harrington, L. B., Kranzusch, P. J., Engelman, A. N., and Doudna, J. A. (2015) Foreign DNA capture during CRISPR-Cas adaptive immunity, Nature, 527, 535-538.

46. Brouns, S. J. J., Jore, M. M., Lundgren, M., Westra, E. R., Slijkhuis, R. J. H., et al. (2008) Small CRISPR RNAs guide antiviral defense in prokaryotes, Science, 321, 960-964.

47. Yosef, I., Goren, M. G., and Qimron, U. (2012) Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli, Nucleic Acids Res., 40, 5569-5576.

48. Datsenko, K. A., Pougach, K., Tikhonov, A., Wanner, B. L., Severinov, K., and Semenova, E. (2012) Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system, Nat. Commun., 3, 1-7.

49. Vorontsova, D., Datsenko, K. A., Medvedeva, S., Bondy-Denomy, J., Savitskaya, E. E., et al. (2015) Foreign DNA acquisition by the IF CRISPR-Cas system requires all components of the interference machinery, Nucleic Acids Res., 43, 10848-10860.

50. Deltcheva, E., Chylinski, K., Sharma, C. M., Gonzales, K., Chao, Y., et al. (2011) CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III, Nature, 471, 602-607.

51. Sapranauskas, R., Gasiunas, G., Fremaux, C., Barrangou, R., Horvath, P., and Siksnys, V. (2011) The Streptococcus thermophilus CRISPR/Cas system provides immunity in Escherichia coli, Nucleic Acids Res., 39, 9275-9282.

52. Hatoum-Aslan, A., Maniv, I., Samai, P., and Marraffini, L. A. (2014) Genetic characterization of antiplasmid immunity through a type III-A CRISPR-Cas system, J. Bacteriol., 196, 310-317.

53. Babu, M., Beloglazova, N., Flick, R., Graham, C., Skarina, T., et al. (2011) A dual function of the CRISPR-Cas system in bacterial antivirus immunity and DNA repair, Mol. Microbiol., 79, 484-502.

54. Wiedenheft, B., Zhou, K., Jinek, M., Coyle, S. M., Ma, W., and Doudna, J. A. (2009) Structural basis for DNase activity of a conserved protein implicated in CRISPR-mediated genome defense, Structure, 17, 904-912.

55. Beloglazova, N., Lemak, S., Flick, R., and Yakunin, A. F. (2015) Analysis of nuclease activity of Cas1 proteins against complex DNA substrates, in CRISPR, Springer, pp. 251-264.

56. Nam, K. H., Ding, F., Haitjema, C., Huang, Q., DeLisa, M. P., and Ke, A. (2012) Double-stranded endonuclease activity in Bacillus halodurans clustered regularly interspaced short palindromic repeats (CRISPR)-associated Cas2 protein, J. Biol. Chem., 287, 35943-35952.

57. Dixit, B., Ghosh, K. K., Fernandes, G., Kumar, P., Gogoi, P., and Kumar, M. (2016) Dual nuclease activity of a Cas2 protein in CRISPR-Cas subtype I-B of Leptospira interrogans, FEBS Lett., 590, 1002-1016.

58. Savitskaya, E. E., Musharova, O. S., and Severinov, K. V (2016) Diversity of CRISPR-Cas-mediated mechanisms of adaptive immunity in prokaryotes and their application in biotechnology, Biochemistry (Moscow), 81, 653-661.

59. Mizuuchi, K., and Adzuma, K. (1991) Inversion of the phosphate chirality at the target site of Mu DNA strand transfer: evidence for a one-step transesterification mechanism, Cell, 66, 129-140.

60. Krupovic, M., Makarova, K. S., Forterre, P., Prangishvili, D., and Koonin, E. V (2014) Casposons: a new superfamily of self-synthesizing DNA transposons at the origin of prokaryotic CRISPR-Cas immunity, BMC Biol., 12, 36.

61. Béguin, P., Charpin, N., Koonin, E. V., Forterre, P., and Krupovic, M. (2016) Casposon integration shows strong target site preference and recapitulates protospacer integration by CRISPR-Cas systems, Nucleic Acids Res., 44, 10367-10376.

62. Rollie, C., Graham, S., Rouillon, C., and White, M. F. (2018) Prespacer processing and specific integration in a type IA CRISPR system, Nucleic Acids Res., 46, 1007-1020.

63. Levy, A., Goren, M. G., Yosef, I., Auster, O., Manor, M., et al. (2015) CRISPR adaptation biases explain preference for acquisition of foreign DNA, Nature, 520, 505-510.

64. Weissman, J. L., Stoltzfus, A., Westra, E. R., and Johnson, P. L. F. (2020) Avoidance of Self during CRISPR Immunization, Trends Microbiol., 28, 543-553, doi: 10.1016/j.tim.2020.02.005.

65. Dorman, C. J., and Bhriain, N. N. (2020) CRISPR-Cas, DNA supercoiling, and nucleoid-associated proteins, Trends Microbiol., 28, 19-27.

66. Kurilovich, E., Shiriaeva, A., Metlitskaya, A., Morozova, N., Ivancic-Bace, I., et al. (2019) Genome maintenance proteins modulate autoimmunity mediated primed adaptation by the Escherichia coli type IE CRISPR-cas system, Genes (Basel), 10, 872.

67. Radovčić, M., Killelea, T., Savitskaya, E., Wettstein, L., Bolt, E. L., and Ivančić-Baće, I. (2018) CRISPR-Cas adaptation in Escherichia coli requires RecBCD helicase but not nuclease activity, is independent of homologous recombination, and is antagonized by 5′ ssDNA exonucleases, Nucleic Acids Res., 46, 10173-10183.

68. Ivančić-Baće, I., Cass, S. D., Wearne, S. J., and Bolt, E. L. (2015) Different genome stability proteins underpin primed and naive adaptation in E. coli CRISPR-Cas immunity, Nucleic Acids Res., 43, 10821-10830.

69. Deveau, H., Barrangou, R., Garneau, J. E., Labonté, J., Fremaux, C., et al. (2008) Phage response to CRISPR-encoded resistance in Streptococcus thermophilus, J. Bacteriol., 190, 1390-1400.

70. Semenova, E., Jore, M. M., Datsenko, K. A., Semenova, A., Westra, E. R., et al. (2011) Interference by clustered regularly interspaced short palindromic repeat (CRISPR) RNA is governed by a seed sequence, Proc. Natl. Acad. Sci. USA, 108, 10098-10103.

71. Fineran, P. C., Gerritzen, M. J. H., Suárez-Diez, M., Künne, T., Boekhorst, J., et al. (2014) Degenerate target sites mediate rapid primed CRISPR adaptation, Proc. Natl. Acad. Sci. USA, 111, E1629-E1638.

72. Westra, E. R., Semenova, E., Datsenko, K. A., Jackson, R. N., Wiedenheft, B., et al. (2013) Type IE CRISPR-cas systems discriminate target from non-target DNA through base pairing-independent PAM recognition, PLoS Genet., 9, e1003742.

73. Richter, C., Dy, R. L., McKenzie, R. E., Watson, B. N. J., Taylor, C., et al. (2014) Priming in the Type IF CRISPR-Cas system triggers strand-independent spacer acquisition, bi-directionally from the primed protospacer, Nucleic Acids Res., 42, 8516-8526.

74. Garrett, S., Shiimori, M., Watts, E. A., Clark, L., Graveley, B. R., and Terns, M. P. (2020) Primed CRISPR DNA uptake in Pyrococcus furiosus, Nucleic Acids Res., 48, 6120-6135.

75. Li, M., Wang, R., and Xiang, H. (2014) Haloarcula hispanica CRISPR authenticates PAM of a target sequence to prime discriminative adaptation, Nucleic Acids Res., 42, 7226-7235.

76. Rao, C., Chin, D., and Ensminger, A. W. (2017) Priming in a permissive type IC CRISPR-Cas system reveals distinct dynamics of spacer acquisition and loss, RNA, 23, 1525-1538.

77. Almendros, C., Nobrega, F. L., McKenzie, R. E., and Brouns, S. J. J. (2019) Cas4–Cas1 fusions drive efficient PAM selection and control CRISPR adaptation, Nucleic Acids Res., 47, 5223-5230.

78. Nussenzweig, P. M., McGinn, J., and Marraffini, L. A. (2019) Cas9 cleavage of viral genomes primes the acquisition of new immunological memories, Cell Host Microbe, 26, 515-526.

79. Savitskaya, E., Semenova, E., Dedkov, V., Metlitskaya, A., and Severinov, K. (2013) High-throughput analysis of type IE CRISPR/Cas spacer acquisition in E. coli, RNA Biol., 10, 716-725.

80. Xue, C., Seetharam, A. S., Musharova, O., Severinov, K., Brouns, S. J., et al. (2015) CRISPR interference and priming varies with individual spacer sequences, Nucleic Acids Res., 43, 10831-10847.

81. Künne, T., Kieper, S. N., Bannenberg, J. W., Vogel, A. I. M., Miellet, W. R., et al. (2016) Cas3-derived target DNA degradation fragments fuel primed CRISPR adaptation, Mol. Cell, 63, 852-864.

82. Dillard, K. E., Brown, M. W., Johnson, N. V., Xiao, Y., Dolan, A., et al. (2018) Assembly and translocation of a CRISPR-Cas primed acquisition complex, Cell, 175, 934-946.

83. Redding, S., Sternberg, S. H., Marshall, M., Gibb, B., Bhat, P., et al. (2015) Surveillance and processing of foreign DNA by the Escherichia coli CRISPR-Cas system, Cell, 163, 854-865.

84. Sashital, D. G., Wiedenheft, B., and Doudna, J. A. (2012) Mechanism of foreign DNA selection in a bacterial adaptive immune system, Mol. Cell, 46, 606-615.

85. Semenova, E., Savitskaya, E., Musharova, O., Strotskaya, A., Vorontsova, D., et al. (2016) Highly efficient primed spacer acquisition from targets destroyed by the Escherichia coli type IE CRISPR-Cas interfering complex, Proc. Natl. Acad. Sci. USA, 113, 7626-7631.

86. Severinov, K., Ispolatov, I., and Semenova, E. (2016) The influence of copy-number of targeted extrachromosomal genetic elements on the outcome of CRISPR-Cas defense, Front. Mol. Biosci., 3, 45.

87. Shabalina, S., and Koonin, E. (2008) Origins and evolution of eukaryotic RNA interference, Trends Ecol. Evol., 23, 578-587.

88. Makarova, K. S., Wolf, Y. I., van der Oost, J., and Koonin, E. V. (2009) Prokaryotic homologs of Argonaute proteins are predicted to function as key components of a novel system of defense against mobile genetic elements., Biol. Direct, 4, 29.

89. Willkomm, S., Makarova, K. S., and Grohmann, D. (2018) DNA silencing by prokaryotic Argonaute proteins adds a new layer of defense against invading nucleic acids, FEMS Microbiol. Rev., 42, 376-387.

90. Kuzmenko, A., Oguienko, A., Esyunina, D., Yudin, D., Petrova, M., et al. (2020) DNA targeting and interference by a bacterial Argonaute nuclease, Nature, 587, 632-637, doi: 10.1038/s41586-020-2605-1.

91. Wang, Y., Juranek, S., Li, H., Sheng, G., Tuschl, T., and Patel, D. J. (2008) Structure of an argonaute silencing complex with a seed-containing guide DNA and target RNA duplex, Nature, 456, 921-926.

92. Olovnikov, I., Chan, K., Sachidanandam, R., Newman, D. K., and Aravin, A. A. (2013) Bacterial argonaute samples the transcriptome to identify foreign DNA, Mol. Cell, 51, 594-605.

93. Lisitskaya, L., Aravin, A. A., and Kulbachinskiy, A. (2018) DNA interference and beyond: structure and functions of prokaryotic Argonaute proteins, Nat. Commun., 9, 1-12.

94. Swarts, D. C., Hegge, J. W., Hinojo, I., Shiimori, M., Ellis, M. A., et al. (2015) Argonaute of the archaeon Pyrococcus furiosus is a DNA-guided nuclease that targets cognate DNA, Nucleic Acids Res., 43, 5120-5129.

95. Kuzmenko, A., Yudin, D., Ryazansky, S., Kulbachinskiy, A., and Aravin, A. A. (2019) Programmable DNA cleavage by Ago nucleases from mesophilic bacteria Clostridium butyricum and Limnothrix rosea, Nucleic Acids Res., 47, 5822-5836.

96. Yuan, Y.-R., Pei, Y., Ma, J.-B., Kuryavyi, V., Zhadina, M., et al. (2005) Crystal structure of A. aeolicus argonaute, a site-specific DNA-guided endoribonuclease, provides insights into RISC-mediated mRNA cleavage, Mol. Cell, 19, 405-419.

97. Wang, Y., Juranek, S., Li, H., Sheng, G., Wardle, G. S., et al. (2009) Nucleation, propagation and cleavage of target RNAs in Ago silencing complexes, Nature, 461, 754-761.

98. Kaya, E., Doxzen, K. W., Knoll, K. R., Wilson, R. C., Strutt, S. C., et al. (2016) A bacterial Argonaute with noncanonical guide RNA specificity, Proc. Natl. Acad. Sci. USA, 113, 4057-4062.

99. Willkomm, S., Zander, A., Gust, A., and Grohmann, D. (2015) A prokaryotic twist on argonaute function, Life, 5, 538-553.

100. Swarts, D. C., Jore, M. M., Westra, E. R., Zhu, Y., Janssen, J. H., et al. (2014) DNA-guided DNA interference by a prokaryotic Argonaute, Nature, 507, 258-261.

101. Ryazansky, S., Kulbachinskiy, A., and Aravin, A. A. (2018) The expanded universe of prokaryotic Argonaute proteins, MBio, 9, e01935-18, doi: 10.1128/mBio.01935-18.

102. Zander, A., Willkomm, S., Ofer, S., Van Wolferen, M., Egert, L., et al. (2017) Guide-independent DNA cleavage by archaeal Argonaute from Methanocaldococcus jannaschii, Nat. Microbiol., 2, 1-10.

103. Swarts, D. C., Szczepaniak, M., Sheng, G., Chandradoss, S. D., Zhu, Y., et al. (2017) Autonomous generation and loading of DNA guides by bacterial Argonaute, Mol. Cell, 65, 985-998.

104. Jolly, S. M., Gainetdinov, I., Jouravleva, K., Zhang, H., Strittmatter, L., et al. (2020) Thermus thermophilus Argonaute functions in the completion of DNA replication, Cell, 182, 1545-1559.

105. Koonin, E. V. (2017) Evolution of RNA- and DNA-guided antivirus defense systems in prokaryotes and eukaryotes: common ancestry vs convergence, Biol. Direct, 12, 1-14.

106. Chopin, M.-C., Chopin, A., and Bidnenko, E. (2005) Phage abortive infection in lactococci: variations on a theme, Curr. Opin. Microbiol., 8, 473-9.

107. Lopatina, A., Tal, N., and Sorek, R. (2020) Abortive infection: bacterial suicide as an antiviral immune strategy, Annu. Rev. Virol., 7, 371-384.

108. Labrie, S. J., Samson, J. E., and Moineau, S. (2010) Bacteriophage resistance mechanisms, Nat. Rev. Microbiol., 8, 317-327.

109. Fukuyo, M., Sasaki, A., and Kobayashi, I. (2012) Success of a suicidal defense strategy against infection in a structured habitat, Sci. Rep., 2, 238.

110. Van Houte, S., Buckling, A., and Westra, E. R. (2016) Evolutionary ecology of prokaryotic immune mechanisms, Microbiol. Mol. Biol. Rev., 80, 745-763.

111. Barrangou, R., and Horvath, P. (2011) Lactic acid bacteria defenses against phages, in Stress Responses of Lactic Acid Bacteria, Springer, pp. 459-478.

112. Durmaz, E., and Klaenhammer, T. R. (2007) Abortive phage resistance mechanism AbiZ speeds the lysis clock to cause premature lysis of phage-infected Lactococcus lactis, J. Bacteriol., 189, 1417-1425.

113. Wang, C., Villion, M., Semper, C., Coros, C., Moineau, S., and Zimmerly, S. (2011) A reverse transcriptase-related protein mediates phage resistance and polymerizes untemplated DNA in vitro, Nucleic Acids Res., 39, 7620-7629.

114. Tangney, M., and Fitzgerald, G. F. (2002) Effectiveness of the lactococcal abortive infection systems AbiA, AbiE, AbiF and AbiG against P335 type phages, FEMS Microbiol. Lett., 210, 67-72.

115. Parreira, R., Ehrlich, S. D., and Chopin, M. (1996) Dramatic decay of phage transcripts in lactococcal cells carrying the abortive infection determinant AbiB, Mol. Microbiol., 19, 221-230.

116. Samson, J. E., Spinelli, S., Cambillau, C., and Moineau, S. (2013) Structure and activity of AbiQ, a lactococcal endoribonuclease belonging to the type III toxin–antitoxin system, Mol. Microbiol., 87, 756-768.

117. Bidnenko, E., Ehrlich, D., and Chopin, M.-C. (1995) Phage operon involved in sensitivity to the Lactococcus lactis abortive infection mechanism AbiD1, J. Bacteriol., 177, 3824-3829.

118. Bouchard, J. D., Dion, E., Bissonnette, F., and Moineau, S. (2002) Characterization of the two-component abortive phage infection mechanism AbiT from Lactococcus lactis, J. Bacteriol., 184, 6325-6332.

119. Haaber, J., Samson, J. E., Labrie, S. J., Campanacci, V., Cambillau, C., et al. (2010) Lactococcal abortive infection protein AbiV interacts directly with the phage protein SaV and prevents translation of phage proteins, Appl. Environ. Microbiol., 76, 7085-7092.

120. Depardieu, F., Didier, J.-P., Bernheim, A., Sherlock, A., Molina, H., et al. (2016) A eukaryotic-like serine/threonine kinase protects staphylococci against phages, Cell Host Microbe, 20, 471-481.

121. Snyder, L. (1995) Phage-exclusion enzymes: a bonanza of biochemical and cell biology reagents? Mol. Microbiol., 15, 415-20.

122. Yu, Y. T., and Snyder, L. (1994) Translation elongation factor Tu cleaved by a phage-exclusion system, Proc. Natl. Acad. Sci. USA, 91, 802-806.

123. Levitz, R., Chapman, D., Amitsur, M., Green, R., Snyder, L., and Kaufmann, G. (1990) The optional E. coli prr locus encodes a latent form of phage T4-induced anticodon nuclease, EMBO J., 9, 1383-1389.

124. Cheng, X., Wang, W., and Molineux, I. J. (2004) F exclusion of bacteriophage T7 occurs at the cell membrane, Virology, 326, 340-352.

125. Schmitt, C. K., Kemp, P., and Molineux, I. J. (1991) Genes 1.2 and 10 of bacteriophages T3 and T7 determine the permeability lesions observed in infected cells of Escherichia coli expressing the F plasmid gene pifA, J. Bacteriol., 173, 6507-6514.

126. Toothman, P., and Herskowitz, I. (1980) Rex-dependent exclusion of lambdoid phages II. Determinants of sensitivity to exclusion, Virology, 102, 147-160.

127. Parma, D. H., Snyder, M., Sobolevski, S., Nawroz, M., Brody, E., and Gold, L. (1992) The Rex system of bacteriophage lambda: tolerance and altruistic cell death, Genes Dev., 6, 497-510.

128. Yamaguchi, Y., Park, J.-H., and Inouye, M. (2011) Toxin–antitoxin systems in bacteria and archaea, Annu. Rev. Genet., 45, 61-79.

129. Page, R., and Peti, W. (2016) Toxin–antitoxin systems in bacterial growth arrest and persistence, Nat. Chem. Biol., 12, 208-214.

130. Makarova, K. S., Wolf, Y. I., and Koonin, E. V. (2013) Comparative genomics of defense systems in archaea and bacteria, Nucleic Acids Res., 41, 4360-4377.

131. Harms, A., Brodersen, D. E., Mitarai, N., and Gerdes, K. (2018) Toxins, targets, and triggers: an overview of toxin–antitoxin biology, Mol. Cell, 70, 768-784.

132. Fineran, P. C., Blower, T. R., Foulds, I. J., Humphreys, D. P., Lilley, K. S., and Salmond, G. P. C. (2009) The phage abortive infection system, ToxIN, functions as a protein–RNA toxin–antitoxin pair, Proc. Natl. Acad. Sci. USA, 106, 894-899.

133. Short, F. L., Akusobi, C., Broadhurst, W. R., and Salmond, G. P. C. (2018) The bacterial Type III toxin–antitoxin system, ToxIN, is a dynamic protein–RNA complex with stability-dependent antiviral abortive infection activity, Sci. Rep., 8, 1-10.

134. Koga, M., Otsuka, Y., Lemire, S., and Yonesaki, T. (2011) Escherichia coli rnlA and rnlB compose a novel toxin–antitoxin system, Genetics, 187, 123-130.

135. Otsuka, Y., and Yonesaki, T. (2012) Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins, Mol. Microbiol., 83, 669-681.

136. Dy, R. L., Przybilski, R., Semeijn, K., Salmond, G. P. C., and Fineran, P. C. (2014) A widespread bacteriophage abortive infection system functions through a type IV toxin–antitoxin mechanism, Nucleic Acids Res., 42, 4590-4605.

137. Cai, Y., Usher, B., Gutierrez, C., Tolcan, A., Mansour, M., Fineran, P. C., et al. (2020) A nucleotidyltransferase toxin inhibits growth of Mycobacterium tuberculosis through inactivation of tRNA acceptor stems, Sci. Adv., 6, eabb6651.

138. Hampton, H. G., Smith, L. M., Ferguson, S., Meaden, S., Jackson, S. A., and Fineran, P. C. (2020) Functional genomics reveals the toxin–antitoxin repertoire and AbiE activity in Serratia, Microb. Genom., 6, mgen000458, doi: 10.1099/mgen.0.000458.

139. Hazan, R., and 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.

140. Pecota, D. C., and Wood, T. K. (1996) Exclusion of T4 phage by the hok/sok killer locus from plasmid R1, J. Bacteriol., 178, 2044-2050.

141. Hayes, F. (2003) Toxins-antitoxins: plasmid maintenance, programmed cell death, and cell cycle arrest, Science, 301, 1496-1499.

142. Koonin, E. V., Makarova, K. S., and Wolf, Y. I. (2017) Evolutionary genomics of defense systems in archaea and bacteria, Annu. Rev. Microbiol., 71, 233-261.

143. Song, S., and Wood, T. K. (2018) Post-segregational killing and phage inhibition are not mediated by cell death through toxin/antitoxin systems, Front. Microbiol., 9, 814.

144. Sberro, H., Fremin, B. J., Zlitni, S., Edfors, F., Greenfield, N., et al. (2019) Large-scale analyses of human microbiomes reveal thousands of small, novel genes, Cell, 178, 1245-1259.e14.

145. Simon, A. J., Ellington, A. D., and Finkelstein, I. J. (2019) Retrons and their applications in genome engineering, Nucleic Acids Res., 47, 11007-11019.

146. Millman, A., Bernheim, A., Stokar-Avihail, A., Fedorenko, T., Voichek, M., et al. (2020) Bacterial retrons function in anti-phage defense, Cell, 183, 1551-1561.e12, doi: 10.1016/j.cell.2020.09.065.

147. Bobonis, J., Mitosch, K., Mateus, A., Kritikos, G., Elfenbein, J. R., et al. (2020) Phage proteins block and trigger retron toxin/antitoxin systems, BioRxiv, doi: 10.1101/2020.06.22.160242.

148. Bobonis, J., Mateus, A., Pfalz, B., Garcia-Santamarina, S., Galardini, M., et al. (2020) Bacterial retrons encode tripartite toxin/antitoxin systems, BioRxiv, doi: 10.1101/2020.06.22.160168.

149. Gao, L., Altae-Tran, H., Böhning, F., Makarova, K. S., Segel, M., et al. (2020) Diverse enzymatic activities mediate antiviral immunity in prokaryotes, Science, 369, 1077-1084.

150. Burroughs, A. M., Zhang, D., Schäffer, D. E., Iyer, L. M., and Aravind, L. (2015) Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling, Nucleic Acids Res., 43, 10633-10654.

151. Cohen, D., Melamed, S., Millman, A., Shulman, G., Oppenheimer-Shaanan, Y., et al. (2019) Cyclic GMP-AMP signalling protects bacteria against viral infection, Nature, 574, 691-695.

152. Whiteley, A. T., Eaglesham, J. B., de Oliveira Mann, C. C., Morehouse, B. R., Lowey, B., et al. (2019) Bacterial cGAS-like enzymes synthesize diverse nucleotide signals, Nature, 567, 194-199.

153. Millman, A., Melamed, S., Amitai, G., and Sorek, R. (2020) Diversity and classification of cyclic-oligonucleotide-based anti-phage signalling systems, Nat. Microbiol., 5, 1608-1615, doi: 10.1038/s41564-020-0777-y.

154. Ablasser, A., and Chen, Z. J. (2019) cGAS in action: expanding roles in immunity and inflammation, Science, 363, eaat8657, doi: 10.1126/science.aat8657.

155. Davies, B. W., Bogard, R. W., Young, T. S., and Mekalanos, J. J. (2012) Coordinated regulation of accessory genetic elements produces cyclic di-nucleotides for V. cholerae virulence, Cell, 149, 358-370.

156. Severin, G. B., Ramliden, M. S., Hawver, L. A., Wang, K., Pell, M. E., et al. (2018) Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae, Proc. Natl. Acad. Sci. USA, 115, E6048-E6055.

157. Yoon, S. H., and Waters, C. M. (2021) The ever-expanding world of bacterial cyclic oligonucleotide second messengers, Curr. Opin. Microbiol., 60, 96-103.

158. Morehouse, B. R., Govande, A. A., Millman, A., Keszei, A. F. A., Lowey, B., et al. (2020) STING cyclic dinucleotide sensing originated in bacteria, Nature, 586, 429-433.

159. Ye, Q., Lau, R. K., Mathews, I. T., Birkholz, E. A., Watrous, J. D., et al. (2020) HORMA domain proteins and a Trip13-like ATPase regulate bacterial cGAS-like enzymes to mediate bacteriophage immunity, Mol. Cell, 77, 709-722.e7.

160. Rosenberg, S. C., and Corbett, K. D. (2015) The multifaceted roles of the HORMA domain in cellular signaling, J. Cell Biol., 211, 745-755.

161. Lau, R. K., Ye, Q., Birkholz, E. A., Berg, K. R., Patel, L., et al. (2020) Structure and mechanism of a cyclic trinucleotide-activated bacterial endonuclease mediating bacteriophage immunity, Mol. Cell, 77, 723-733.e6.

162. Lowey, B., Whiteley, A. T., Keszei, A. F. A., Morehouse, B. R., Mathews, I. T., et al. (2020) CBASS immunity uses CARF-related effectors to sense 3′-5′-and 2′-5′-linked cyclic oligonucleotide signals and protect bacteria from phage infection, Cell, 182, 38-49.

163. Casjens, S. (2003) Prophages and bacterial genomics: what have we learned so far? Mol. Microbiol., 49, 277-300.

164. Canchaya, C., Proux, C., Fournous, G., Bruttin, A., and Brüssow, H. (2003) Prophage genomics, Microbiol. Mol. Biol. Rev., 67, 238-276.

165. Bondy-Denomy, J., Qian, J., Westra, E. R., Buckling, A., Guttman, D. S., et al. (2016) Prophages mediate defense against phage infection through diverse mechanisms, ISME J., 10, 2854-2866.

166. Dedrick, R. M., Jacobs-Sera, D., Bustamante, C. A. G., Garlena, R. A., Mavrich, T. N., et al. (2017) Prophage-mediated defence against viral attack and viral counter-defence, Nat. Microbiol., 2, 1-13.

167. Roux, S., Krupovic, M., Daly, R. A., Borges, A. L., Nayfach, S., et al. (2019) Cryptic inoviruses revealed as pervasive in bacteria and archaea across Earth’s biomes, Nat. Microbiol., 4, 1895-1906.

168. Benler, S., and Koonin, E. V (2020) Phage lysis-lysogeny switches and programmed cell death: danse macabre, BioEssays, 42, e2000114, doi: 10.1002/bies.202000114.

169. Waldor, M. K., and Friedman, D. I. (2005) Phage regulatory circuits and virulence gene expression, Curr. Opin. Microbiol., 8, 459-465.

170. Juhala, R. J., Ford, M. E., Duda, R. L., Youlton, A., Hatfull, G. F., and Hendrix, R. W. (2000) Genomic sequences of bacteriophages HK97 and HK022: pervasive genetic mosaicism in the lambdoid bacteriophages, J. Mol. Biol., 299, 27-51.

171. Taylor, V. L., Fitzpatrick, A. D., Islam, Z., and Maxwell, K. L. (2019) The diverse impacts of phage morons on bacterial fitness and virulence, in Advances in Virus Research, Elsevier, Vol. 103, pp. 1-31.

172. Newton, G. J., Daniels, C., Burrows, L. L., Kropinski, A. M., Clarke, A. J., and Lam, J. S. (2001) Three-component-mediated serotype conversion in Pseudomonas aeruginosa by bacteriophage D3, Mol. Microbiol., 39, 1237-1247.

173. Krylov, S. V, Kropinski, A. M., Shaburova, O. V, Miroshnikov, K. A., Chesnokova, E. N., and Krylov, V. N. (2013) New temperate Pseudomonas aeruginosa phage, phi297: specific features of genome structure, Russ. J. Genet., 49, 806-818.

174. Taylor, V. L., Hoage, J. F. J., Thrane, S. W., Huszczynski, S. M., Jelsbak, L., and Lam, J. S. (2016) A bacteriophage-acquired O-antigen polymerase (Wzyβ) from P. aeruginosa serotype O16 performs a varied mechanism compared to its cognate Wzyα, Front. Microbiol., 7, 393.

175. Lehane, A. M., Korres, H., and Verma, N. K. (2005) Bacteriophage-encoded glucosyltransferase GtrII of Shigella flexneri: membrane topology and identification of critical residues, Biochem. J., 389, 137-143.

176. Perry, L. L., SanMiguel, P., Minocha, U., Terekhov, A. I., Shroyer, M. L., et al. (2009) Sequence analysis of Escherichia coli O157: H7 bacteriophage ΦV10 and identification of a phage-encoded immunity protein that modifies the O157 antigen, FEMS Microbiol. Lett., 292, 182-186.

177. Gentile, G. M., Wetzel, K. S., Dedrick, R. M., Montgomery, M. T., Garlena, R. A., et al. (2019) More evidence of collusion: a new prophage-mediated viral defense system encoded by mycobacteriophage sbash, MBio, 10, e00196-19, doi: 10.1128/mBio.00196-19.

178. Montgomery, M. T., Guerrero Bustamante, C. A., Dedrick, R. M., Jacobs-Sera, D., and Hatfull, G. F. (2019) Yet more evidence of collusion: a new viral defense system encoded by gordonia phage carolann, MBio, 10, 1-18.

179. Jimmy, S., Saha, C. K., Kurata, T., Stavropoulos, C., Oliveira, S. R. A., et al. (2020) A widespread toxin–antitoxin system exploiting growth control via alarmone signaling, Proc. Natl. Acad. Sci. USA, 117, 10500-10510.

180. Ferullo, D. J., and Lovett, S. T. (2008) The stringent response and cell cycle arrest in Escherichia coli, PLoS Genet., 4, e1000300.

181. Owen, S. V, Wenner, N., Dulberger, C. L., Rodwell, E. V., Bowers-Barnard, A., et al. (2020) Prophage-encoded phage defence proteins with cognate self-immunity, bioRxiv, doi: 10.1101/2020.07.13.199331.

182. Rousset, F., Dowding, J., Bernheim, A., Rocha, E., and Bikard, D. (2021) Prophage-encoded hotspots of bacterial immune systems, bioRxiv, doi: 10.1101/2021.01.21.427644.

183. Atanasiu, C., Su, T. J., Sturrock, S. S., and Dryden, D. T. F. (2002) Interaction of the ocr gene 0.3 protein of bacteriophage T7 with EcoKl restriction/modification enzyme, Nucleic Acids Res., 30, 3936-3944.

184. Isaev, A., Drobiazko, A., Sierro, N., Gordeeva, J., Yosef, I., et al. (2020) Phage T7 DNA mimic protein Ocr is a potent inhibitor of BREX defence, Nucleic Acids Res., 48, 5397-5406.

185. Penadés, J. R., and Christie, G. E. (2015) The phage-inducible chromosomal islands: a family of highly evolved molecular parasites, Annu. Rev. Virol., 2, 181-201.

186. Christie, G. E., and Dokland, T. (2012) Pirates of the Caudovirales, Virology, 434, 210-221.

187. Dokland, T. (2019) Molecular piracy: redirection of bacteriophage capsid assembly by mobile genetic elements, Viruses, 11, 1003.

188. Fillol-Salom, A., Miguel-Romero, L., Marina, A., Chen, J., and Penadés, J. R. (2020) Beyond the CRISPR-Cas safeguard: PICI-encoded innate immune systems protect bacteria from bacteriophage predation, Curr. Opin. Microbiol., 56, 52-58.

189. Novick, R. P., Christie, G. E., and Penadés, J. R. (2010) The phage-related chromosomal islands of Gram-positive bacteria, Nat. Rev. Microbiol., 8, 541-551.

190. Fillol-Salom, A., Martínez-Rubio, R., Abdulrahman, R. F., Chen, J., Davies, R., and Penadés, J. R. (2018) Phage-inducible chromosomal islands are ubiquitous within the bacterial universe, ISME J., 12, 2114-2128.

191. Mitarai, N. (2020) How pirate phage interferes with helper phage: comparison of the two distinct strategies, J. Theor. Biol., 486, 110096.

192. Novick, R. P. (2019) Pathogenicity islands and their role in staphylococcal biology, Microbiol. Spectr., 7, doi: 10.1128/microbiolspec.GPP3-0062-2019.

193. Tormo-Más, M. Á., Mir, I., Shrestha, A., Tallent, S. M., Campoy, S., Lasa, Í., et al. (2010) Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands, Nature, 465, 779-782.

194. Mir-Sanchis, I., Martínez-Rubio, R., Martí, M., Chen, J., Lasa, Í., et al. (2012) Control of Staphylococcus aureus pathogenicity island excision, Mol. Microbiol., 85, 833-845.

195. Ram, G., Chen, J., Kumar, K., Ross, H. F., Ubeda, C., et al. (2012) Staphylococcal pathogenicity island interference with helper phage reproduction is a paradigm of molecular parasitism, Proc. Natl. Acad. Sci. USA, 109, 16300-5.

196. Ram, G., Chen, J., Ross, H. F., and Novick, R. P. (2014) Precisely modulated pathogenicity island interference with late phage gene transcription, Proc. Natl. Acad. Sci. USA, 111, 14536-14541.

197. Martínez-Rubio, R., Quiles-Puchalt, N., Martí, M., Humphrey, S., Ram, G., et al. (2017) Phage-inducible islands in the Gram-positive cocci, ISME J., 11, 1029-1042.

198. Fillol-Salom, A., Bacarizo, J., Alqasmi, M., Ciges-Tomas, J. R., Martínez-Rubio, R., et al. (2019) Hijacking the hijackers: Escherichia coli pathogenicity islands redirect helper phage packaging for their own benefit, Mol. Cell, 75, 1020-1030.

199. O’Hara, B. J., Barth, Z. K., McKitterick, A. C., and Seed, K. D. (2017) A highly specific phage defense system is a conserved feature of the Vibrio cholerae mobilome, PLoS Genet., 13, 1-17.

200. McKitterick, A. C., and Seed, K. D. (2018) Anti-phage islands force their target phage to directly mediate island excision and spread, Nat. Commun., 9, 1-8.

201. McKitterick, A. C., Hays, S. G., Johura, F. T., Alam, M., and Seed, K. D. (2019) Viral satellites exploit phage proteins to escape degradation of the bacterial host chromosome, Cell Host Microbe, 26, 504-514.e4.

202. Barth, Z. K., Silvas, T. V, Angermeyer, A., and Seed, K. D. (2020) Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction, Nucleic Acids Res., 48, 249-263.

203. Barth, Z. K., Netter, Z., Angermeyer, A., Bhardwaj, P., and Seed, K. D. (2020) A family of viral satellites manipulates invading virus gene expression and can affect cholera toxin mobilization, mSystems, 5, e00358-20, doi: 10.1128/mSystems.00358-20.

204. Hays, S. G., and Seed, K. D. (2020) Dominant Vibrio cholerae phage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite, Elife, 9, e53200.

205. McKitterick, A. C., LeGault, K. N., Angermeyer, A., Alam, M., and Seed, K. D. (2019) Competition between mobile genetic elements drives optimization of a phage-encoded CRISPR-Cas system: insights from a natural arms race, Philos. Trans. R. Soc. B, 374, 20180089.

206. Makarova, K. S., Wolf, Y. I., Snir, S., and Koonin, E. V. (2011) Defense islands in bacterial and archaeal genomes and prediction of novel defense systems, J. Bacteriol., 193, 6039-6056.

207. Doron, S., Melamed, S., Ofir, G., Leavitt, A., Lopatina, A., et al. (2018) Systematic discovery of antiphage defense systems in the microbial pangenome, Science, 359, eaar4120, doi: 10.1126/science.aar4120.

208. Burroughs, A. M., and Aravind, L. (2020) Identification of uncharacterized components of prokaryotic immune systems and their diverse eukaryotic reformulations, J. Bacteriol., 202, e00365-20, doi: 10.1128/JB.00365-20.

209. Santiveri, M., Roa-Eguiara, A., Kuhne, C., Wadhwa, N., Berg, H. C., et al. (2020) Structure and function of stator units of the bacterial flagellar motor, Cell, 183, 244-257.

210. Ofir, G., Herbst, E., Baroz, M., Cohen, D., Millman, A., et al. (2021) Antiviral activity of bacterial TIR domains via signaling molecules that trigger cell death, bioRxiv, doi: 10.1101/2021.01.06.425286.

211. Ka, D., Oh, H., Park, E., Kim, J., and Bae, E. (2020) Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD+ degradation, Nat. Commun., 11, 2816, doi: 10.1038/s41467-020-16703-w.

212. Bayless, A. M., and Nishimura, M. T. (2020) Enzymatic functions for Toll/Interleukin-1 receptor domain proteins in the plant immune system, Front. Genet., 11, 539.

213. Badrinarayanan, A., Le, T. B. K., and Laub, M. T. (2015) Bacterial chromosome organization and segregation, Annu. Rev. Cell Dev. Biol., 31, 171-199.

214. Panas, M. W., Jain, P., Yang, H., Mitra, S., Biswas, D., et al. (2014) Noncanonical SMC protein in Mycobacterium smegmatis restricts maintenance of Mycobacterium fortuitum plasmids, Proc. Natl. Acad. Sci. USA, 111, 13264-13271.

215. Pace, H. C., and Brenner, C. (2001) The nitrilase superfamily: classification, structure and function, Genome Biol., 2, 1-9.

216. Mekhedov, S. L., Makarova, K. S., and Koonin, E. V. (2017) The complex domain architecture of SAMD9 family proteins, predicted STAND-like NTPases, suggests new links to inflammation and apoptosis, Biol. Direct, 12, 13.

217. Forsberg, K. J., and Malik, H. S. (2018) Microbial genomics: the expanding universe of bacterial defense systems, Curr. Biol., 28, R361-R364.

218. Van, V., and Van Valen, L. (1973) A New Evolutionary Law, The University of Chicago, Illinois.

219. Stern, A., and Sorek, R. (2011) The phage-host arms race: shaping the evolution of microbes, Bioessays, 33, 43-51.

220. Paterson, S., Vogwill, T., Buckling, A., Benmayor, R., Spiers, A. J., et al. (2010) Antagonistic coevolution accelerates molecular evolution, Nature, 464, 275-278.

221. Ignacio-Espinoza, J. C., Ahlgren, N. A., and Fuhrman, J. A. (2020) Long-term stability and Red Queen-like strain dynamics in marine viruses, Nat. Microbiol., 5, 265-271.

222. Furuta, Y., Kawai, M., Uchiyama, I., and Kobayashi, I. (2011) Domain movement within a gene: a novel evolutionary mechanism for protein diversification, PLoS One, 6, e18819.

223. Dupuis, M.- È., Villion, M., Magadán, A. H., and Moineau, S. (2013) CRISPR-Cas and restriction-modification systems are compatible and increase phage resistance, Nat. Commun., 4, 1-7.

224. Hynes, A. P., Villion, M., and Moineau, S. (2014) Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages, Nat. Commun., 5, 1-6.

225. Bernheim, A., and Sorek, R. (2020) The pan-immune system of bacteria: antiviral defence as a community resource, Nat. Rev. Microbiol., 18, 113-119.

226. Koonin, E. V., Makarova, K. S., Wolf, Y. I., and Krupovic, M. (2020) Evolutionary entanglement of mobile genetic elements and host defence systems: guns for hire, Nat. Rev. Genet., 21, 119-131.

227. Høyland-Kroghsbo, N. M., Paczkowski, J., Mukherjee, S., Broniewski, J., Westra, E., et al. (2017) Quorum sensing controls the Pseudomonas aeruginosa CRISPR-Cas adaptive immune system, Proc. Natl. Acad. Sci. USA, 114, 131-135.

228. Xiong, L., Liu, S., Chen, S., Xiao, Y., Zhu, B., et al. (2019) A new type of DNA phosphorothioation-based antiviral system in archaea, Nat. Commun., 10, 1-11.

229. Al-Shayeb, B., Sachdeva, R., Chen, L.-X., Ward, F., Munk, P., et al. (2020) Clades of huge phages from across Earth’s ecosystems, Nature, 578, 425-431.