1887

Microbiology

Volume 165, Issue 8

Resistance is not futile: bacterial ‘innate’ and CRISPR-Cas ‘adaptive’ immune systems Free

Abstract

Bacteria are under a constant pressure from their viruses (phages) and other mobile genetic elements. They protect themselves through a range of defence strategies, which can be broadly classified as ‘innate’ and ‘adaptive’. The bacterial innate immune systems include defences provided by restriction modification and abortive infection, among others. Bacterial adaptive immunity is elicited by a diverse range of CRISPR-Cas systems. Here, I discuss our research on both innate and adaptive phage resistance mechanisms and some of the evasion strategies employed by phages.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): abortive infection , bacteriophages , CRISPR-Cas , phage resistance and toxin-antitoxin
© 2019 The Authors
Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.000802
2019-08-01
2021-10-17
Loading full text...

Full text loading...

/deliver/fulltext/micro/165/8/834.html?itemId=/content/journal/micro/10.1099/mic.0.000802&mimeType=html&fmt=ahah

References

  1. Salmond GP, Fineran PC. A century of the phage: past, present and future. Nat Rev Microbiol 2015; 13:777–786 [View Article]
     [Google Scholar]
  2. Dy RL, Richter C, Salmond GP, Fineran PC. Remarkable mechanisms in microbes to resist phage infections. Annu Rev Virol 2014b; 1:307–331 [View Article]
     [Google Scholar]
  3. Dy RL, Rigano LA, Fineran PC. Phage-based biocontrol strategies and their application in agriculture and aquaculture. Biochem Soc Trans 2018; 46:1605–1613 [View Article]
     [Google Scholar]
  4. Frampton RA, Pitman AR, Fineran PC. Advances in bacteriophage-mediated control of plant pathogens. Int J Microbiol 2012; 2012:1–11 [View Article]
     [Google Scholar]
  5. Frampton RA, Taylor C, Holguín Moreno AV, Visnovsky SB, Petty NK et al. Identification of bacteriophages for biocontrol of the kiwifruit canker phytopathogen Pseudomonas syringae pv. actinidiae. Appl Environ Microbiol 2014; 80:2216–2228 [View Article]
     [Google Scholar]
  6. Frampton RA, Acedo EL, Young VL, Chen D, Tong B et al. Genome, proteome and structure of a T7-like bacteriophage of the kiwifruit canker phytopathogen Pseudomonas syringae pv. actinidiae. Viruses 2015; 7:3361–3379 [View Article]
     [Google Scholar]
  7. Barrangou R, Doudna JA. Applications of CRISPR technologies in research and beyond. Nat Biotechnol 2016; 34:933–941 [View Article]
     [Google Scholar]
  8. Fineran PC, Dy RL. Gene regulation by engineered CRISPR-Cas systems. Curr Opin Microbiol 2014; 18:83–89 [View Article]
     [Google Scholar]
  9. Knott GJ, Doudna JA. CRISPR-Cas guides the future of genetic engineering. Science 2018; 361:866–869 [View Article]
     [Google Scholar]
  10. Luria SE, Delbrück M. Mutations of bacteria from virus sensitivity to virus resistance. Genetics 1943; 28:491–511
     [Google Scholar]
  11. Hershey AD, Chase M. Independent functions of viral protein and nucleic acid in growth of bacteriophage. J Gen Physiol 1952; 36:39–56 [View Article]
     [Google Scholar]
  12. Benzer S. Fine structure of a genetic region in bacteriophage. Proc Natl Acad Sci U S A 1955; 41:344–354 [View Article]
     [Google Scholar]
  13. Sanger F, Air GM, Barrell BG, Brown NL, Coulson AR et al. Nucleotide sequence of bacteriophage phi X174 DNA. Nature 1977; 265:687–695 [View Article]
     [Google Scholar]
  14. Bertani G, Weigle JJ. Host controlled variation in bacterial viruses. J Bacteriol 1953; 65:113–121
     [Google Scholar]
  15. Luria SE, Human ML. A nonhereditary, host-induced variation of bacterial viruses. J Bacteriol 1952; 64:557–569
     [Google Scholar]
  16. Petty NK, Evans TJ, Fineran PC, Salmond GP. Biotechnological exploitation of bacteriophage research. Trends Biotechnol 2007; 25:7–15 [View Article]
     [Google Scholar]
  17. Fineran PC, Blower TR, Foulds IJ, Humphreys DP, Lilley KS et al. The phage abortive infection system, toxin, functions as a protein-RNA toxin-antitoxin pair. Proc Natl Acad Sci U S A 2009; 106:894–899 [View Article]
     [Google Scholar]
  18. Cook GM, Robson JR, Frampton RA, McKenzie J, Przybilski R et al. Ribonucleases in bacterial toxin-antitoxin systems. Biochim Biophys Acta 2013; 1829:523–531 [View Article]
     [Google Scholar]
  19. Blower TR, Fineran PC, Johnson MJ, Toth IK, Humphreys DP et al. Mutagenesis and functional characterization of the RNA and protein components of the toxIN abortive infection and toxIN-antitoxin locus of Erwinia . J Bacteriol 2009; 191:6029–6039 [View Article]
     [Google Scholar]
  20. Blower TR, Short FL, Rao F, Mizuguchi K, Pei XY et al. Identification and classification of bacterial type III toxin-antitoxin systems encoded in chromosomal and plasmid genomes. Nucleic Acids Res 2012c; 40:6158–6173 [View Article]
     [Google Scholar]
  21. Blower TR, Pei XY, Short FL, Fineran PC, Humphreys DP et al. A processed noncoding RNA regulates an altruistic bacterial antiviral system. Nat Struct Mol Biol 2011; 18:185–190 [View Article]
     [Google Scholar]
  22. Short FL, Pei XY, Blower TR, Ong S-L, Fineran PC et al. Selectivity and self-assembly in the control of a bacterial toxin by an antitoxic noncoding RNA pseudoknot. Proc Natl Acad Sci U S A 2013; 110:E241–E249 [View Article]
     [Google Scholar]
  23. Blower TR, Evans TJ, Przybilski R, Fineran PC, Salmond GP. Viral evasion of a bacterial suicide system by RNA-based molecular mimicry enables infectious altruism. PLoS Genet 2012a; 8:e1003023 [View Article]
     [Google Scholar]
  24. Blower TR, Short FL, Fineran PC, Salmond GP. Viral molecular mimicry circumvents abortive infection and suppresses bacterial suicide to make hosts permissive for replication. Bacteriophage 2012b; 2:234–238 [View Article]
     [Google Scholar]
  25. Blower TR, Chai R, Przybilski R, Chindhy S, Fang X et al. Evolution of Pectobacterium bacteriophage ΦM1 to escape two bifunctional type III toxin-antitoxin and abortive infection systems through mutations in a single viral gene. Appl Environ Microbiol 2017; 83: 2017 04 15 [View Article]
     [Google Scholar]
  26. Dy RL, Przybilski R, Semeijn K, Salmond GP, Fineran PC. A widespread bacteriophage abortive infection system functions through a type IV toxin-antitoxin mechanism. Nucleic Acids Res 2014a; 42:4590–4605 [View Article]
     [Google Scholar]
  27. Hampton HG, Jackson SA, Fagerlund RD, Vogel AIM, Dy RL et al. AbiEi binds cooperatively to the type IV abiE Toxin–Antitoxin operator via a positively-charged surface and causes DNA bending and negative autoregulation. J Mol Biol 2018; 430:1141–1156 [View Article]
     [Google Scholar]
  28. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P et al. CRISPR provides acquired resistance against viruses in prokaryotes. Science 2007; 315:1709–1712 [View Article]
     [Google Scholar]
  29. Makarova KS, Wolf YI, Alkhnbashi OS, Costa F, Shah SA et al. An updated evolutionary classification of CRISPR–Cas systems. Nat Rev Microbiol 2015; 13:722–736 [View Article]
     [Google Scholar]
  30. Richter C, Chang JT, Fineran PC. Function and regulation of clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR associated (Cas) systems. Viruses 2012a; 4:2291–2311 [View Article]
     [Google Scholar]
  31. Fineran PC, Charpentier E. Memory of viral infections by CRISPR-Cas adaptive immune systems: acquisition of new information. Virology 2012; 434:202–209 [View Article]
     [Google Scholar]
  32. Jackson SA, McKenzie RE, Fagerlund RD, Kieper SN, Fineran PC et al. CRISPR-Cas: adapting to change. Science 2017; 356:eaal5056 [View Article]
     [Google Scholar]
  33. Shmakov S, Smargon A, Scott D, Cox D, Pyzocha N et al. Diversity and evolution of class 2 CRISPR–Cas systems. Nat Rev Microbiol 2017; 15:169–182 [View Article]
     [Google Scholar]
  34. Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 2014; 346:1258096 [View Article]
     [Google Scholar]
  35. Sternberg SH, Doudna JA. Expanding the biologist's toolkit with CRISPR-Cas9. Mol Cell 2015; 58:568–574 [View Article]
     [Google Scholar]
  36. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337:816–821 [View Article]
     [Google Scholar]
  37. Fagerlund RD, Staals RHJ, Fineran PC. The Cpf1 CRISPR-Cas protein expands genome-editing tools. Genome Biol 2015; 16:251 [View Article]
     [Google Scholar]
  38. Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS et al. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 2015; 163:759–771 [View Article]
     [Google Scholar]
  39. Abudayyeh OO, Gootenberg JS, Essletzbichler P, Han S, Joung J et al. RNA targeting with CRISPR-Cas13. Nature 2017; 550:280–284 [View Article]
     [Google Scholar]
  40. East-Seletsky A, O'Connell MR, Knight SC, Burstein D, Cate JHD et al. Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection. Nature 2016; 538:270–273 [View Article]
     [Google Scholar]
  41. Bell KS, Sebaihia M, Pritchard L, Holden MTG, Hyman LJ et al. Genome sequence of the enterobacterial phytopathogen Erwinia carotovora subsp. atroseptica and characterization of virulence factors. Proc Natl Acad Sci U S A 2004; 101:11105–11110 [View Article]
     [Google Scholar]
  42. Fineran PC, Iglesias Cans MC, Ramsay JP, Wilf NM, Cossyleon D et al. Draft genome sequence of Serratia sp. strain ATCC 39006, a model bacterium for analysis of the biosynthesis and regulation of prodigiosin, a carbapenem, and gas vesicles. Genome Announc 2013; 1:e01039–01013 [View Article]
     [Google Scholar]
  43. Amitai G, Sorek R. CRISPR–Cas adaptation: insights into the mechanism of action. Nat Rev Microbiol 2016; 14:67–76 [View Article]
     [Google Scholar]
  44. Sternberg SH, Richter H, Charpentier E, Qimron U. Adaptation in CRISPR-Cas systems. Mol Cell 2016; 61:797–808 [View Article]
     [Google Scholar]
  45. Yosef I, Goren MG, Qimron U. Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli . Nucleic Acids Res 2012; 40:5569–5576 [View Article]
     [Google Scholar]
  46. Richter C, Gristwood T, Clulow JS, Fineran PC. In vivo protein interactions and complex formation in the Pectobacterium atrosepticum subtype I-F CRISPR/Cas system. PLoS One 2012b; 7:e49549 [View Article]
     [Google Scholar]
  47. Nuñez JK, Harrington LB, Kranzusch PJ, Engelman AN, Doudna JA. Foreign DNA capture during CRISPR-Cas adaptive immunity. Nature 2015a; 527:535–538 [View Article]
     [Google Scholar]
  48. Nuñez JK, Lee ASY, Engelman A, Doudna JA. Integrase-mediated spacer acquisition during CRISPR–Cas adaptive immunity. Nature 2015b; 519:193–198 [View Article]
     [Google Scholar]
  49. Wilkinson ME, Nakatani Y, Staals RH, Kieper SN, Opel-Reading HK et al. Structural plasticity and in vivo activity of Cas1 from the type I-F CRISPR-Cas system. Biochem J 2016; 473:1063–1072 [View Article]
     [Google Scholar]
  50. Fagerlund RD, Wilkinson ME, Klykov O, Barendregt A, Pearce FG et al. Spacer capture and integration by a type I-F Cas1-Cas2-3 CRISPR adaptation complex. Proc Natl Acad Sci U S A 2017; 114:E5122–E5128 [View Article]
     [Google Scholar]
  51. Fagerlund RD, Ferguson TJ, Maxwell HWR, Opel-Reading HK, Krause KL et al. Reconstitution of CRISPR adaptation in vitro and its detection by PCR. Methods Enzymol 2019; 616:411–433 [View Article]
     [Google Scholar]
  52. Patterson AG, Yevstigneyeva MS, Fineran PC. Regulation of CRISPR-Cas adaptive immune systems. Curr Opin Microbiol 2017; 37:1–7 [View Article]
     [Google Scholar]
  53. Patterson AG, Chang JT, Taylor C, Fineran PC. Regulation of the type I-F CRISPR-Cas system by CRP-cAMP and GalM controls spacer acquisition and interference. Nucleic Acids Res 2015; 43:6038–6048 [View Article]
     [Google Scholar]
  54. Patterson AG, Jackson SA, Taylor C, Evans GB, Salmond GPC et al. Quorum sensing controls adaptive immunity through the regulation of multiple CRISPR-Cas systems. Mol Cell 2016; 64:1102–1108 [View Article]
     [Google Scholar]
  55. Brouns SJJ, Jore MM, Lundgren M, Westra ER, Slijkhuis RJH et al. Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 2008; 321:960–964 [View Article]
     [Google Scholar]
  56. Carte J, Wang R, Li H, Terns RM, Terns MP. Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes. Genes Dev 2008; 22:3489–3496 [View Article]
     [Google Scholar]
  57. Przybilski R, Richter C, Gristwood T, Clulow JS, Vercoe RB et al. Csy4 is responsible for CRISPR RNA processing in Pectobacterium atrosepticum . RNA Biol 2011; 8:517–528 [View Article]
     [Google Scholar]
  58. Biswas A, Gagnon JN, Brouns SJJ, Fineran PC, Brown CM. CRISPRTarget: bioinformatic prediction and analysis of crRNA targets. RNA Biol 2013; 10:817–827 [View Article]
     [Google Scholar]
  59. Biswas A, Fineran PC, Brown CM. Computational detection of CRISPR/crRNA targets. Methods Mol Biol 2015; 1311:77–89 [View Article]
     [Google Scholar]
  60. Biswas A, Fineran PC, Brown CM. Accurate computational prediction of the transcribed strand of CRISPR non-coding RNAs. Bioinformatics 2014; 30:1805–1813 [View Article]
     [Google Scholar]
  61. Biswas A, Staals RH, Morales SE, Fineran PC, Brown CM. CRISPRDetect: a flexible algorithm to define CRISPR arrays. BMC Genomics 2016; 17:356 [View Article]
     [Google Scholar]
  62. Vercoe RB, Chang JT, Dy RL, Taylor C, Gristwood T et al. Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and Expel or remodel pathogenicity islands. PLoS Genet 2013; 9:e1003454 [View Article]
     [Google Scholar]
  63. Staals RHJ, Jackson SA, Biswas A, Brouns SJJ, Brown CM et al. Interference-driven spacer acquisition is dominant over naive and primed adaptation in a native CRISPR-Cas system. Nat Commun 2016; 7:12853 [View Article]
     [Google Scholar]
  64. Panda P, Vanga BR, Lu A, Fiers M, Fineran PC et al. Pectobacterium atrosepticum and Pectobacterium carotovorum harbor distinct, independently acquired integrative and conjugative elements encoding coronafacic acid that enhance virulence on potato stems. Front Microbiol 2016; 7: [View Article]
     [Google Scholar]
  65. Dy RL, Pitman AR, Fineran PC. Chromosomal targeting by CRISPR-Cas systems can contribute to genome plasticity in bacteria. Mob Genet Elements 2013; 3:e26831 [View Article]
     [Google Scholar]
  66. Westra ER, Buckling A, Fineran PC. CRISPR–Cas systems: beyond adaptive immunity. Nat Rev Microbiol 2014; 12:317–326 [View Article]
     [Google Scholar]
  67. Hampton HG, McNeil MB, Paterson TJ, Ney B, Williamson NR et al. CRISPR-Cas gene-editing reveals RsmA and RsmC act through FlhDC to repress the SdhE flavinylation factor and control motility and prodigiosin production in Serratia . Microbiology 2016; 162:1047–1058 [View Article]
     [Google Scholar]
  68. Bikard D, Euler CW, Jiang W, Nussenzweig PM, Goldberg GW et al. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nat Biotechnol 2014; 32:1146–1150 [View Article]
     [Google Scholar]
  69. Citorik RJ, Mimee M, Lu TK. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat Biotechnol 2014; 32:1141–1145 [View Article]
     [Google Scholar]
  70. Gomaa AA, Klumpe HE, Luo ML, Selle K, Barrangou R et al. Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems. MBio 2014; 5:e00928–00913 [View Article]
     [Google Scholar]
  71. Fineran PC, Gerritzen MJH, Suárez-Diez M, Künne T, Boekhorst J et al. Degenerate target sites mediate rapid primed CRISPR adaptation. Proc Natl Acad Sci U S A 2014; 111:E1629–E1638 [View Article]
     [Google Scholar]
  72. Watson BNJ, Easingwood RA, Tong B, Wolf M, Salmond GPC et al. Different genetic and morphological outcomes for phages targeted by single or multiple CRISPR-Cas spacers. Philos Trans R Soc Lond B Biol Sci 2019; 374:20180090 [View Article]
     [Google Scholar]
  73. Datsenko KA, Pougach K, Tikhonov A, Wanner BL, Severinov K et al. Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system. Nat Commun 2012; 3:945 [View Article]
     [Google Scholar]
  74. Richter C, Dy RL, McKenzie RE, Watson BNJ, Taylor C et al. Priming in the type I-F CRISPR-Cas system triggers strand-independent spacer acquisition, bi-directionally from the primed protospacer. Nucleic Acids Res 2014; 42:8516–8526 [View Article]
     [Google Scholar]
  75. Swarts DC, Mosterd C, van Passel MWJ, Brouns SJJ. CRISPR interference directs strand specific spacer acquisition. PLoS One 2012; 7:e35888 [View Article]
     [Google Scholar]
  76. Jackson SA, Birkholz N, Malone LM, Fineran PC. Imprecise spacer acquisition generates CRISPR-Cas immune diversity through primed adaptation. Cell Host Microbe 2019; 25:e254250–260 [View Article]
     [Google Scholar]
  77. van Houte S, Ekroth AKE, Broniewski JM, Chabas H, Ashby B et al. The diversity-generating benefits of a prokaryotic adaptive immune system. Nature 2016; 532:385–388 [View Article]
     [Google Scholar]
  78. Nicholson TJ, Jackson SA, Croft BI, Staals RH, Fineran PC et al. Bioinformatic evidence of widespread priming in type I and II CRISPR-Cas systems. RNA Biol 2018; 15:1–11 [View Article]
     [Google Scholar]
  79. Bondy-Denomy J, Pawluk A, Maxwell KL, Davidson AR. Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system. Nature 2013; 493:429–432 [View Article]
     [Google Scholar]
  80. Pawluk A, Bondy-Denomy J, Cheung VHW, Maxwell KL, Davidson AR. A new group of phage anti-CRISPR genes inhibits the type I-E CRISPR-Cas system of Pseudomonas aeruginosa . MBio 2014; 5:e00896 [View Article]
     [Google Scholar]
  81. Bondy-Denomy J, Davidson AR, Doudna JA, Fineran PC, Maxwell KL et al. A unified resource for tracking anti-CRISPR names. Crispr J 2018; 1:304–305 [View Article]
     [Google Scholar]
  82. Pawluk A, Staals RHJ, Taylor C, Watson BNJ, Saha S et al. Inactivation of CRISPR-Cas systems by anti-CRISPR proteins in diverse bacterial species. Nat Microbiol 2016; 1:16085 [View Article]
     [Google Scholar]
  83. Silas S, Lucas-Elio P, Jackson SA, Aroca-Crevillén A, Hansen LL et al. Type III CRISPR-Cas systems can provide redundancy to counteract viral escape from type I systems. Elife 2017; 6: [View Article]
     [Google Scholar]
  84. Watson BNJ, Staals RHJ, Fineran PC. CRISPR-Cas-Mediated phage resistance enhances horizontal gene transfer by transduction. MBio 2018; 9: [View Article]
     [Google Scholar]
  85. Palmer KL, Gilmore MS. Multidrug-resistant enterococci lack CRISPR-Cas. MBio 2010; 1:e00227-10 2010 Oct 12 [View Article]
     [Google Scholar]
  86. Shehreen S, Chyou T-Y, Fineran PC, Brown CM. Genome-wide correlation analysis suggests different roles of CRISPR-Cas systems in the acquisition of antibiotic resistance genes in diverse species. Philos Trans R Soc Lond B Biol Sci 2019; 374:20180384 [View Article]
     [Google Scholar]
  87. van Belkum A, Soriaga LB, LaFave MC, Akella S, Veyrieras J-B et al. Phylogenetic distribution of CRISPR-Cas systems in antibiotic-resistant Pseudomonas aeruginosa . MBio 2015; 6:e01796–01715 [View Article]
     [Google Scholar]
  88. Fineran PC. CRISPR-Cas impedes archaeal mating. Nat Microbiol 2019; 4:2–3 [View Article]
     [Google Scholar]
  89. Turgeman-Grott I, Joseph S, Marton S, Eizenshtein K, Naor A et al. Pervasive acquisition of CRISPR memory driven by inter-species mating of archaea can limit gene transfer and influence speciation. Nat Microbiol 2019; 4:177–186 [View Article]
     [Google Scholar]
  90. Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A et al. Systematic discovery of antiphage defense systems in the microbial pangenome. Science 2018; 359:eaar4120 [View Article]
     [Google Scholar]
  91. Kronheim S, Daniel-Ivad M, Duan Z, Hwang S, Wong AI et al. A chemical defence against phage infection. Nature 2018; 564:283–286 [View Article]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.000802
Loading
Resistance is not futile: bacterial ‘innate’ and CRISPR-Cas ‘adaptive’ immune systems
Microbiology 165, 834 (2019); https://doi.org/10.1099/mic.0.000802
/content/journal/micro/10.1099/mic.0.000802
/content/journal/micro/10.1099/mic.0.000802
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error