CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems are prokaryotic adaptive immune systems that provide protection against infection by parasitic mobile genetic elements, such as viruses and plasmids. CRISPR-Cas systems are found in approximately half of all sequenced bacterial genomes and in nearly all archaeal genomes. In this review, we summarize our current understanding of the evolutionary ecology of CRISPR-Cas systems, highlight their value as model systems to answer fundamental questions concerning host–parasite coevolution, and explain how CRISPR-Cas systems can be useful tools for scientists across virtually all disciplines.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Agari Y, Sakamoto K, Tamakoshi M, Oshima T, Kuramitsu S, Shinkai A. 2010. Transcription profile of Thermus thermophilus CRISPR systems after phage infection. J. Mol. Biol. 395:270–81 [Google Scholar]
  2. Agrawal A, Lively CM. 2002. Infection genetics: gene-for-gene versus matching-alleles models and all points in between. Evol. Ecol. Res. 4:79–90 [Google Scholar]
  3. Amitai G, Sorek R. 2016. CRISPR-Cas adaptation: insights into the mechanism of action. Nat. Rev. Microbiol. 14:67–76 [Google Scholar]
  4. Anderson RE, Brazelton WJ, Baross JA. 2011. Using CRISPRs as a metagenomic tool to identify microbial hosts of a diffuse flow hydrothermal vent viral assemblage. FEMS Microbiol. Ecol. 77:120–33 [Google Scholar]
  5. Andersson AF, Banfield JF. 2008. Virus population dynamics and acquired virus resistance in natural microbial communities. Science 320:1047–50 [Google Scholar]
  6. Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P. et al. 2007. CRISPR provides acquired resistance against viruses in prokaryotes. Science 315:1709–12 [Google Scholar]
  7. Berg Miller ME, Yeoman CJ, Chia N, Tringe SG, Angly FE. et al. 2012. Phage-bacteria relationships and CRISPR elements revealed by a metagenomic survey of the rumen microbiome. Environ. Microbiol. 14:207–27 [Google Scholar]
  8. Bikard D, Euler CW, Jiang W, Nussenzweig PM, Goldberg GW. et al. 2014. Exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials. Nat. Biotechnol. 32:1146–50 [Google Scholar]
  9. Bikard D, Hatoum-Aslan A, Mucida D, Marraffini LA. 2012. CRISPR interference can prevent natural transformation and virulence acquisition during in vivo bacterial infection. Cell Host Microbe 12:177–86 [Google Scholar]
  10. Blosser TR, Loeff L, Westra ER, Vlot M, Kunne T. et al. 2015. Two distinct DNA binding modes guide dual roles of a CRISPR-Cas protein complex. Mol. Cell 58:60–70 [Google Scholar]
  11. Bondy-Denomy J, Garcia B, Strum S, Du M, Rollins MF. et al. 2015. Multiple mechanisms for CRISPR-Cas inhibition by anti-CRISPR proteins. Nature 526:136–39 [Google Scholar]
  12. Bondy-Denomy J, Pawluk A, Maxwell KL, Davidson AR. 2013. Bacteriophage genes that inactivate the CRISPR/Cas bacterial immune system. Nature 493:429–32 [Google Scholar]
  13. Breitbart M, Hewson I, Felts B, Mahaffy JM, Nulton J. et al. 2003. Metagenomic analyses of an uncultured viral community from human feces. J. Bacteriol. 185:6220–23 [Google Scholar]
  14. Cady KC, White AS, Hammond JH, Abendroth MD, Karthikeyan RS. et al. 2011. Prevalence, conservation and functional analysis of Yersinia and Escherichia CRISPR regions in clinical Pseudomonas aeruginosa isolates. Microbiology 157:430–37 [Google Scholar]
  15. Champer J, Buchman A, Akbari OS. 2016. Cheating evolution: engineering gene drives to manipulate the fate of wild populations. Nat. Rev. Genet. 17:146–59 [Google Scholar]
  16. Charpentier E, Richter H, van der Oost J, White MF. 2015. Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR-Cas adaptive immunity. FEMS Microbiol. Rev. 39:428–41 [Google Scholar]
  17. Childs LM, England WE, Young MJ, Weitz JS, Whitaker RJ. 2014. CRISPR-induced distributed immunity in microbial populations. PLOS ONE 9:e101710 [Google Scholar]
  18. Chylinski K, Makarova KS, Charpentier E, Koonin EV. 2014. Classification and evolution of type II CRISPR-Cas systems. Nucleic Acids Res 42:6091–105 [Google Scholar]
  19. Citorik RJ, Mimee M, Lu TK. 2014. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat. Biotechnol. 32:1141–45 [Google Scholar]
  20. Cui Y, Li Y, Gorge O, Platonov ME, Yan Y. et al. 2008. Insight into microevolution of Yersinia pestis by clustered regularly interspaced short palindromic repeats. PLOS ONE 3:e2652 [Google Scholar]
  21. Datsenko KA, Pougach K, Tikhonov A, Wanner BL, Severinov K, Semenova E. 2012. Molecular memory of prior infections activates the CRISPR/Cas adaptive bacterial immunity system. Nat. Commun. 3:945 [Google Scholar]
  22. DeBoy RT, Mongodin EF, Emerson JB, Nelson KE. 2006. Chromosome evolution in the Thermotogales: large-scale inversions and strain diversification of CRISPR sequences. J. Bacteriol. 188:2364–74 [Google Scholar]
  23. Delaney NF, Balenger S, Bonneaud C, Marx CJ, Hill GE. et al. 2012. Ultrafast evolution and loss of CRISPRs following a host shift in a novel wildlife pathogen. Mycoplasma gallisepticum. PLOS Genet. 8:e1002511 [Google Scholar]
  24. Delannoy S, Beutin L, Burgos Y, Fach P. 2012a. Specific detection of enteroaggregative hemorrhagic Escherichia coli O104:H4 strains by use of the CRISPR locus as a target for a diagnostic real-time PCR. J. Clin. Microbiol. 50:3485–92 [Google Scholar]
  25. Delannoy S, Beutin L, Fach P. 2012b. Use of clustered regularly interspaced short palindromic repeat sequence polymorphisms for specific detection of enterohemorrhagic Escherichia coli strains of serotypes O26:H11, O45:H2, O103:H2, O111:H8, O121:H19, O145:H28, and O157:H7 by real-time PCR. J. Clin. Microbiol. 50:4035–40 [Google Scholar]
  26. Deltcheva E, Chylinski K, Sharma CM, Gonzales K, Chao Y. et al. 2011. CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III. Nature 471:602–7 [Google Scholar]
  27. Deveau H, Barrangou R, Garneau JE, Labonte J, Fremaux C. et al. 2008. Phage response to CRISPR-encoded resistance in Streptococcus thermophilus. J. Bacteriol. 190:1390–400 [Google Scholar]
  28. DiCarlo JE, Chavez A, Dietz SL, Esvelt KM, Church GM. 2015. Safeguarding CRISPR-Cas9 gene drives in yeast. Nat. Biotechnol. 33:1250–55 [Google Scholar]
  29. Dupuis ME, Villion M, Magadan AH, Moineau S. 2013. CRISPR-Cas and restriction-modification systems are compatible and increase phage resistance. Nat. Commun. 4:2087 [Google Scholar]
  30. Emerson JB, Andrade K, Thomas BC, Norman A, Allen EE. et al. 2013. Virus-host and CRISPR dynamics in Archaea-dominated hypersaline Lake Tyrrell, Victoria, Australia. Archaea 2013:370871 [Google Scholar]
  31. Erdmann S, Garrett RA. 2012. Selective and hyperactive uptake of foreign DNA by adaptive immune systems of an archaeon via two distinct mechanisms. Mol. Microbiol. 85:1044–56 [Google Scholar]
  32. Esvelt KM, Smidler AL, Catteruccia F, Church GM. 2014. Concerning RNA-guided gene drives for the alteration of wild populations. eLife 3:e03401 [Google Scholar]
  33. Fineran PC, Gerritzen MJ, Suarez-Diez M, Kunne T, Boekhorst J. et al. 2014. Degenerate target sites mediate rapid primed CRISPR adaptation. PNAS 111:E1629–38 [Google Scholar]
  34. Fonfara I, Richter H, Bratovič M, Le Rhun A, Charpentier E. 2016. The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA. Nature 532:517–21 [Google Scholar]
  35. Gandon S, Vale PF. 2014. The evolution of resistance against good and bad infections. J. Evol. Biol. 27:303–12 [Google Scholar]
  36. Gantz VM, Bier E. 2015. Genome editing. The mutagenic chain reaction: a method for converting heterozygous to homozygous mutations. Science 348:442–44 [Google Scholar]
  37. Gantz VM, Jasinskiene N, Tatarenkova O, Fazekas A, Macias VM. et al. 2015. Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi. PNAS 112:E6736–43 [Google Scholar]
  38. Garneau JE, Dupuis ME, Villion M, Romero DA, Barrangou R. et al. 2010. The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Nature 468:67–71 [Google Scholar]
  39. Garrett RA, Prangishvili D, Shah SA, Reuter M, Stetter KO, Peng X. 2010. Metagenomic analyses of novel viruses and plasmids from a cultured environmental sample of hyperthermophilic neutrophiles. Environ. Microbiol. 12:2918–30 [Google Scholar]
  40. Godde JS, Bickerton A. 2006. The repetitive DNA elements called CRISPRs and their associated genes: evidence of horizontal transfer among prokaryotes. J. Mol. Evol. 62:718–29 [Google Scholar]
  41. Gogleva AA, Gelfand MS, Artamonova II. 2014. Comparative analysis of CRISPR cassettes from the human gut metagenomic contigs. BMC Genom 15:202 [Google Scholar]
  42. Goldberg GW, Marraffini LA. 2015. Resistance and tolerance to foreign elements by prokaryotic immune systems—curating the genome. Nat. Rev. Immunol. 15:717–24 [Google Scholar]
  43. Gophna U, Kristensen DM, Wolf YI, Popa O, Drevet C, Koonin EV. 2015. No evidence of inhibition of horizontal gene transfer by CRISPR-Cas on evolutionary timescales. ISME J 9:2021–27 [Google Scholar]
  44. Grissa I, Vergnaud G, Pourcel C. 2007. The CRISPRdb database and tools to display CRISPRs and to generate dictionaries of spacers and repeats. BMC Bioinform 8:172 [Google Scholar]
  45. Gunderson FF, Cianciotto NP. 2013. The CRISPR-associated gene cas2 of Legionella pneumophila is required for intracellular infection of amoebae. mBio 4:e00074–13 [Google Scholar]
  46. Gunderson FF, Mallama CA, Fairbairn SG, Cianciotto NP. 2015. Nuclease activity of Legionella pneumophila Cas2 promotes intracellular infection of amoebal host cells. Infect. Immun. 83:1008–18 [Google Scholar]
  47. Haft DH, Selengut J, Mongodin EF, Nelson KE. 2005. A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes. PLOS Comput. Biol. 1:e60 [Google Scholar]
  48. Hamilton R, Siva-Jothy M, Boots M. 2008. Two arms are better than one: Parasite variation leads to combined inducible and constitutive innate immune responses. Proc. R. Soc. B 275:937–45 [Google Scholar]
  49. Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C. et al. 2016. A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae. Nat. Biotechnol. 34:78–83 [Google Scholar]
  50. Hatfull GF, Hendrix RW. 2011. Bacteriophages and their genomes. Curr. Opin. Virol. 1:298–303 [Google Scholar]
  51. Hatoum-Aslan A, Marraffini LA. 2014. Impact of CRISPR immunity on the emergence and virulence of bacterial pathogens. Curr. Opin. Microbiol. 17C:82–90 [Google Scholar]
  52. He F, Chen L, Peng X. 2014. First experimental evidence for the presence of a CRISPR toxin in Sulfolobus. J. Mol. Biol. 426:3683–88 [Google Scholar]
  53. Heidelberg JF, Nelson WC, Schoenfeld T, Bhaya D. 2009. Germ warfare in a microbial mat community: CRISPRs provide insights into the co-evolution of host and viral genomes. PLOS ONE 4:e4169 [Google Scholar]
  54. Held NL, Herrera A, Cadillo-Quiroz H, Whitaker RJ. 2010. CRISPR associated diversity within a population of Sulfolobus islandicus. PLOS ONE 5:e12988 [Google Scholar]
  55. Held NL, Herrera A, Whitaker RJ. 2013. Reassortment of CRISPR repeat-spacer loci in Sulfolobus islandicus. Environ. Microbiol. 15:3065–76 [Google Scholar]
  56. Held NL, Whitaker RJ. 2009. Viral biogeography revealed by signatures in Sulfolobus islandicus genomes. Environ. Microbiol. 11:457–66 [Google Scholar]
  57. Heler R, Samai P, Modell JW, Weiner C, Goldberg GW. et al. 2015. Cas9 specifies functional viral targets during CRISPR-Cas adaptation. Nature 519:199–202 [Google Scholar]
  58. Heussler GE, Cady KC, Koeppen K, Bhuju S, Stanton BA, O'Toole GA. 2015. Clustered regularly interspaced short palindromic repeat-dependent, biofilm-specific death of Pseudomonas aeruginosa mediated by increased expression of phage-related genes. mBio 6:e00129 [Google Scholar]
  59. Horvath P, Coute-Monvoisin AC, Romero DA, Boyaval P, Fremaux C, Barrangou R. 2009. Comparative analysis of CRISPR loci in lactic acid bacteria genomes. Int. J. Food Microbiol. 131:62–70 [Google Scholar]
  60. Horvath P, Romero DA, Coute-Monvoisin AC, Richards M, Deveau H. et al. 2008. Diversity, activity, and evolution of CRISPR loci in Streptococcus thermophilus. J. Bacteriol. 190:1401–12 [Google Scholar]
  61. Hynes AP, Villion M, Moineau S. 2014. Adaptation in bacterial CRISPR-Cas immunity can be driven by defective phages. Nat. Commun. 5:4399 [Google Scholar]
  62. Iranzo J, Lobkovsky AE, Wolf YI, Koonin EV. 2013. Evolutionary dynamics of the prokaryotic adaptive immunity system CRISPR-Cas in an explicit ecological context. J. Bacteriol. 195:3834–44 [Google Scholar]
  63. Ishino Y, Shinagawa H, Makino K, Amemura M, Nakata A. 1987. Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in. Escherichia coli , and identification of the gene product. J. Bacteriol 169:5429–33 [Google Scholar]
  64. Jackson RN, Wiedenheft B. 2015. A conserved structural chassis for mounting versatile CRISPR RNA-guided immune responses. Mol. Cell 58:722–28 [Google Scholar]
  65. Jiang W, Maniv I, Arain F, Wang Y, Levin BR, Marraffini LA. 2013. Dealing with the evolutionary downside of CRISPR immunity: bacteria and beneficial plasmids. PLOS Genet 9:e1003844 [Google Scholar]
  66. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337:816–21 [Google Scholar]
  67. Kennedy EM, Cullen BR. 2015. Bacterial CRISPR/Cas DNA endonucleases: A revolutionary technology that could dramatically impact viral research and treatment. Virology 479–480:213–20 [Google Scholar]
  68. Killip MJ, Fodor E, Randall RE. 2015. Influenza virus activation of the interferon system. Virus Res 209:11–22 [Google Scholar]
  69. Koonin EV, Makarova KS. 2013. CRISPR-Cas: evolution of an RNA-based adaptive immunity system in prokaryotes. RNA Biol 10:679–86 [Google Scholar]
  70. Koonin EV, Wolf YI. 2009. Is evolution Darwinian or/and Lamarckian. Biol. Direct. 4:42 [Google Scholar]
  71. Koonin EV, Wolf YI. 2016. Just how Lamarckian is CRISPR-Cas immunity: The continuum of evolvability mechanisms. Biol. Direct. 11:9 [Google Scholar]
  72. Krupovic M, Makarova KS, Forterre P, Prangishvili D, Koonin EV. 2014. Casposons: a new superfamily of self-synthesizing DNA transposons at the origin of prokaryotic CRISPR-Cas immunity. BMC Biol 12:36 [Google Scholar]
  73. Krupovic M, Shmakov S, Makarova KS, Forterre P, Koonin EV. 2016. Recent mobility of casposons, self-synthesizing transposons at the origin of the CRISPR-Cas immunity. Genome Biol. Evol. 8:375–86 [Google Scholar]
  74. Kunin V, He S, Warnecke F, Peterson SB, Garcia Martin H. et al. 2008. A bacterial metapopulation adapts locally to phage predation despite global dispersal. Genome Res 18:293–97 [Google Scholar]
  75. Kwon AR, Kim JH, Park SJ, Lee KY, Min YH. et al. 2012. Structural and biochemical characterization of HP0315 from Helicobacter pylori as a VapD protein with an endoribonuclease activity. Nucleic Acids Res 40:4216–28 [Google Scholar]
  76. Levin BR. 2010. Nasty viruses, costly plasmids, population dynamics, and the conditions for establishing and maintaining CRISPR-mediated adaptive immunity in bacteria. PLOS Genet 6:e1001171 [Google Scholar]
  77. Lillestol RK, Redder P, Garrett RA, Brugger K. 2006. A putative viral defence mechanism in archaeal cells. Archaea 2:59–72 [Google Scholar]
  78. Lively CM. 2010. The effect of host genetic diversity on disease spread. Am. Nat. 175:E149–52 [Google Scholar]
  79. Lopez-Sanchez MJ, Sauvage E, Da Cunha V, Clermont D, Ratsima Hariniaina E. et al. 2012. The highly dynamic CRISPR1 system of Streptococcus agalactiae controls the diversity of its mobilome. Mol. Microbiol. 85:1057–71 [Google Scholar]
  80. Louwen R, Horst-Kreft D, de Boer AG, van der Graaf L, de Knegt G. et al. 2013. A novel link between Campylobacter jejuni bacteriophage defence, virulence and Guillain-Barre syndrome. Eur. J. Clin. Microbiol. Infect. Dis. 32:207–26 [Google Scholar]
  81. Makarova KS, Anantharaman V, Aravind L, Koonin EV. 2012. Live virus-free or die: coupling of antivirus immunity and programmed suicide or dormancy in prokaryotes. Biol. Direct. 7:40 [Google Scholar]
  82. Makarova KS, Aravind L, Wolf YI, Koonin EV. 2011a. Unification of Cas protein families and a simple scenario for the origin and evolution of CRISPR-Cas systems. Biol. Direct. 6:38 [Google Scholar]
  83. Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV. 2006. A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biol. Direct. 1:7 [Google Scholar]
  84. Makarova KS, Haft DH, Barrangou R, Brouns SJ, Charpentier E. et al. 2011b. Evolution and classification of the CRISPR-Cas systems. Nat. Rev. Microbiol. 9:467–77 [Google Scholar]
  85. Makarova KS, Wolf YI, Alkhnbashi OS, Costa F, Shah SA. et al. 2015. An updated evolutionary classification of CRISPR-Cas systems. Nat. Rev. Microbiol. 13:722–36 [Google Scholar]
  86. Makarova KS, Wolf YI, Koonin EV. 2013. The basic building blocks and evolution of CRISPR-CAS systems. Biochem. Soc. Trans. 41:1392–400 [Google Scholar]
  87. Mandin P, Repoila F, Vergassola M, Geissmann T, Cossart P. 2007. Identification of new noncoding RNAs in Listeria monocytogenes and prediction of mRNA targets. Nucleic Acids Res 35:962–74 [Google Scholar]
  88. Marraffini LA, Sontheimer EJ. 2008. CRISPR interference limits horizontal gene transfer in staphylococci by targeting DNA. Science 322:1843–45 [Google Scholar]
  89. Marraffini LA, Sontheimer EJ. 2010. Self versus non-self discrimination during CRISPR RNA-directed immunity. Nature 463:568–71 [Google Scholar]
  90. Minot S, Bryson A, Chehoud C, Wu GD, Lewis JD, Bushman FD. 2013. Rapid evolution of the human gut virome. PNAS 110:12450–55 [Google Scholar]
  91. Minot S, Sinha R, Chen J, Li H, Keilbaugh SA. et al. 2011. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res 21:1616–25 [Google Scholar]
  92. Minot S, Wu GD, Lewis JD, Bushman FD. 2012. Conservation of gene cassettes among diverse viruses of the human gut. PLOS ONE 7:e42342 [Google Scholar]
  93. Mojica FJ, Diez-Villasenor C, Garcia-Martinez J, Soria E. 2005. Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements. J. Mol. Evol. 60:174–82 [Google Scholar]
  94. Paez-Espino D, Morovic W, Sun CL, Thomas BC, Ueda K. et al. 2013. Strong bias in the bacterial CRISPR elements that confer immunity to phage. Nat. Commun. 4:1430 [Google Scholar]
  95. Paez-Espino D, Sharon I, Morovic W, Stahl B, Thomas BC. et al. 2015. CRISPR immunity drives rapid phage genome evolution in Streptococcus thermophilus. mBio 6:e00262 [Google Scholar]
  96. Paganelli FL, Willems RJ, Leavis HL. 2012. Optimizing future treatment of enterococcal infections: attacking the biofilm. Trends Microbiol 20:40–49 [Google Scholar]
  97. Palmer KL, Gilmore MS. 2010. Multidrug-resistant enterococci lack CRISPR-cas. mBio 1:e00227 [Google Scholar]
  98. Pawluk A, Bondy-Denomy J, Cheung VH, Maxwell KL, Davidson AR. 2014. A new group of phage anti-CRISPR genes inhibits the type I-E CRISPR-Cas system of Pseudomonas aeruginosa. mBio 5:e00896 [Google Scholar]
  99. Pedulla ML, Ford ME, Houtz JM, Karthikeyan T, Wadsworth C. et al. 2003. Origins of highly mosaic mycobacteriophage genomes. Cell 113:171–82 [Google Scholar]
  100. Pourcel C, Salvignol G, Vergnaud G. 2005. CRISPR elements in Yersinia pestis acquire new repeats by preferential uptake of bacteriophage DNA, and provide additional tools for evolutionary studies. Microbiology 151:653–63 [Google Scholar]
  101. Pride DT, Salzman J, Relman DA. 2012. Comparisons of clustered regularly interspaced short palindromic repeats and viromes in human saliva reveal bacterial adaptations to salivary viruses. Environ. Microbiol. 14:2564–76 [Google Scholar]
  102. Pride DT, Sun CL, Salzman J, Rao N, Loomer P. et al. 2011. Analysis of streptococcal CRISPRs from human saliva reveals substantial sequence diversity within and between subjects over time. Genome Res 21:126–36 [Google Scholar]
  103. Quax TE, Voet M, Sismeiro O, Dillies MA, Jagla B. et al. 2013. Massive activation of archaeal defense genes during viral infection. J. Virol. 87:8419–28 [Google Scholar]
  104. Redding S, Sternberg SH, Marshall M, Gibb B, Bhat P. et al. 2015. Surveillance and processing of foreign DNA by the Escherichia coli CRISPR-Cas system. Cell 163:854–65 [Google Scholar]
  105. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC. et al. 2010. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466:334–38 [Google Scholar]
  106. Reyes A, Semenkovich NP, Whiteson K, Rohwer F, Gordon JI. 2012. Going viral: next-generation sequencing applied to phage populations in the human gut. Nat. Rev. Microbiol. 10:607–17 [Google Scholar]
  107. Rho M, Wu YW, Tang H, Doak TG, Ye Y. 2012. Diverse CRISPRs evolving in human microbiomes. PLOS Genet 8:e1002441 [Google Scholar]
  108. Richter C, Dy RL, McKenzie RE, Watson BN, Taylor C. et al. 2014. Priming in the Type I-F CRISPR-Cas system triggers strand-independent spacer acquisition, bi-directionally from the primed protospacer. Nucleic Acids Res 42:8516–26 [Google Scholar]
  109. Rohwer F. 2003. Global phage diversity. Cell 113:141 [Google Scholar]
  110. Rollins MF, Schuman JT, Paulus K, Bukhari HS, Wiedenheft B. 2015. Mechanism of foreign DNA recognition by a CRISPR RNA-guided surveillance complex from Pseudomonas aeruginosa. Nucleic Acids Res 43:2216–22 [Google Scholar]
  111. Sampson TR, Napier BA, Schroeder MR, Louwen R, Zhao J. et al. 2014. A CRISPR-Cas system enhances envelope integrity mediating antibiotic resistance and inflammasome evasion. PNAS 111:11163–68 [Google Scholar]
  112. Sampson TR, Saroj SD, Llewellyn AC, Tzeng YL, Weiss DS. 2013. A CRISPR/Cas system mediates bacterial innate immune evasion and virulence. Nature 497:254–57 [Google Scholar]
  113. Sampson TR, Weiss DS. 2013. Degeneration of a CRISPR/Cas system and its regulatory target during the evolution of a pathogen. RNA Biol 10:1618–22 [Google Scholar]
  114. Sanguino L, Franqueville L, Vogel TM, Larose C. 2015. Linking environmental prokaryotic viruses and their host through CRISPRs. FEMS Microbiol. Ecol. 91:fiv046 [Google Scholar]
  115. Schouls LM, Reulen S, Duim B, Wagenaar JA, Willems RJ. et al. 2003. Comparative genotyping of Campylobacter jejuni by amplified fragment length polymorphism, multilocus sequence typing, and short repeat sequencing: strain diversity, host range, and recombination. J. Clin. Microbiol. 41:15–26 [Google Scholar]
  116. Shariat N, Dudley EG. 2014. CRISPRs: molecular signatures used for pathogen subtyping. Appl. Environ. Microbiol. 80:430–39 [Google Scholar]
  117. Shmakov S, Abudayyeh OO, Makarova KS, Wolf YI, Gootenberg JS. et al. 2015. Discovery and functional characterization of diverse class 2 CRISPR-Cas systems. Mol. Cell 60:385–97 [Google Scholar]
  118. Smedile F, Messina E, La Cono V, Tsoy O, Monticelli LS. et al. 2013. Metagenomic analysis of hadopelagic microbial assemblages thriving at the deepest part of Mediterranean Sea, Matapan-Vavilov Deep. Environ. Microbiol. 15:167–82 [Google Scholar]
  119. Snyder JC, Bateson MM, Lavin M, Young MJ. 2010. Use of cellular CRISPR (clusters of regularly interspaced short palindromic repeats) spacer-based microarrays for detection of viruses in environmental samples. Appl. Environ. Microbiol. 76:7251–58 [Google Scholar]
  120. Sorokin VA, Gelfand MS, Artamonova II. 2010. Evolutionary dynamics of clustered irregularly interspaced short palindromic repeat systems in the ocean metagenome. Appl. Environ. Microbiol. 76:2136–44 [Google Scholar]
  121. Stern A, Keren L, Wurtzel O, Amitai G, Sorek R. 2010. Self-targeting by CRISPR: gene regulation or autoimmunity. Trends Genet 26:335–40 [Google Scholar]
  122. Stern A, Mick E, Tirosh I, Sagy O, Sorek R. 2012. CRISPR targeting reveals a reservoir of common phages associated with the human gut microbiome. Genome Res 22:1985–94 [Google Scholar]
  123. Sternberg SH, Doudna JA. 2015. Expanding the biologist's toolkit with CRISPR-Cas9. Mol. Cell 58:568–74 [Google Scholar]
  124. Sternberg SH, Redding S, Jinek M, Greene EC, Doudna JA. 2014. DNA interrogation by the CRISPR RNA-guided endonuclease Cas9. Nature 507:62–67 [Google Scholar]
  125. Swarts DC, Mosterd C, van Passel MW, Brouns SJ. 2012. CRISPR interference directs strand specific spacer acquisition. PLOS ONE 7:e35888 [Google Scholar]
  126. Takeuchi N, Wolf YI, Makarova KS, Koonin EV. 2012. Nature and intensity of selection pressure on CRISPR-associated genes. J. Bacteriol. 194:1216–25 [Google Scholar]
  127. Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H. et al. 2009. The Listeria transcriptional landscape from saprophytism to virulence. Nature 459:950–96 [Google Scholar]
  128. Touchon M, Rocha EP. 2010. The small, slow and specialized CRISPR and anti-CRISPR of Escherichia. Salmonella. PLOS ONE 5:e11126 [Google Scholar]
  129. Tyson GW, Banfield JF. 2008. Rapidly evolving CRISPRs implicated in acquired resistance of microorganisms to viruses. Environ. Microbiol. 10:200–7 [Google Scholar]
  130. Vale PF, Lafforgue G, Gatchitch F, Gardan R, Moineau S, Gandon S. 2015. Costs of CRISPR-Cas-mediated resistance in Streptococcus thermophilus. Proc. R. Soc. B 282:20151270 [Google Scholar]
  131. Vale PF, Little TJ. 2010. CRISPR-mediated phage resistance and the ghost of coevolution past. Proc. R. Soc. B 277:2097–103 [Google Scholar]
  132. van Belkum A, Soriaga LB, LaFave MC, Akella S, Veyrieras JB. et al. 2015. Phylogenetic distribution of CRISPR-Cas systems in antibiotic-resistant Pseudomonas aeruginosa. mBio 6:e01796 [Google Scholar]
  133. van der Oost J, Westra ER, Jackson RN, Wiedenheft B. 2014. Unravelling the structural and mechanistic basis of CRISPR-Cas systems. Nat. Rev. Microbiol. 12:479–92 [Google Scholar]
  134. van der Ploeg JR. 2009. Analysis of CRISPR in Streptococcus mutans suggests frequent occurrence of acquired immunity against infection by M102-like bacteriophages. Microbiology 155:1966–76 [Google Scholar]
  135. van Embden JD, van Gorkom T, Kremer K, Jansen R, van Der Zeijst BA, Schouls LM. 2000. Genetic variation and evolutionary origin of the direct repeat locus of Mycobacterium tuberculosis complex bacteria. J. Bacteriol. 182:2393–401 [Google Scholar]
  136. van Houte S, Ekroth AK, Broniewski JM, Chabas H, Ben A. et al. 2016. The diversity-generating benefits of a prokaryotic adaptive immune system. Nature 532:385–88 [Google Scholar]
  137. Vercoe RB, Chang JT, Dy RL, Taylor C, Gristwood T. et al. 2013. Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands. PLOS Genet 9:e1003454 [Google Scholar]
  138. Vergnaud G, Li Y, Gorge O, Cui Y, Song Y. et al. 2007. Analysis of the three Yersinia pestis CRISPR loci provides new tools for phylogenetic studies and possibly for the investigation of ancient DNA. Adv. Exp. Med. Biol 603327–38 [Google Scholar]
  139. Voorhies AA, Eisenlord SD, Marcus DN, Duhaime MB, Biddanda BA. et al. 2015. Ecological and genetic interactions between cyanobacteria and viruses in a low-oxygen mat community inferred through metagenomics and metatranscriptomics. Environ. Microbiol. 18:358–71 [Google Scholar]
  140. Vorontsova D, Datsenko KA, Medvedeva S, Bondy-Denomy J, Savitskaya EE. et al. 2015. Foreign DNA acquisition by the I-F CRISPR-Cas system requires all components of the interference machinery. Nucleic Acids Res 43:10848–60 [Google Scholar]
  141. Wang Z, Pan Q, Gendron P, Zhu W, Guo F. et al. 2016. CRISPR/Cas9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Cell Rep 15:481–89 [Google Scholar]
  142. Weinberger AD, Sun CL, Plucinski MM, Denef VJ, Thomas BC. et al. 2012a. Persisting viral sequences shape microbial CRISPR-based immunity. PLOS Comput. Biol. 8:e1002475 [Google Scholar]
  143. Weinberger AD, Wolf YI, Lobkovsky AE, Gilmore MS, Koonin EV. 2012b. Viral diversity threshold for adaptive immunity in prokaryotes. mBio 3:e00456 [Google Scholar]
  144. Westra ER, Buckling A, Fineran PC. 2014. CRISPR-Cas systems: beyond adaptive immunity. Nat. Rev. Microbiol. 12:317–26 [Google Scholar]
  145. Westra ER, Semenova E, Datsenko KA, Jackson RN, Wiedenheft B. et al. 2013. Type I-E CRISPR-cas systems discriminate target from non-target DNA through base pairing-independent PAM recognition. PLOS Genet 9:e1003742 [Google Scholar]
  146. Westra ER, van Erp PB, Kunne T, Wong SP, Staals RH. et al. 2012. CRISPR immunity relies on the consecutive binding and degradation of negatively supercoiled invader DNA by Cascade and Cas3. Mol. Cell 46:595–605 [Google Scholar]
  147. Westra ER, van Houte S, Oyesiku-Blakemore S, Makin B, Broniewski JM. et al. 2015. Parasite exposure drives selective evolution of constitutive versus inducible defense. Curr. Biol. 25:1043–49 [Google Scholar]
  148. Wiedenheft B, Sternberg SH, Doudna JA. 2012. RNA-guided genetic silencing systems in bacteria and archaea. Nature 482:331–38 [Google Scholar]
  149. Wright AV, Nunez JK, Doudna JA. 2016. Biology and applications of CRISPR systems: harnessing nature's toolbox for genome engineering. Cell 164:29–44 [Google Scholar]
  150. Yosef I, Goren MG, Qimron U. 2012. Proteins and DNA elements essential for the CRISPR adaptation process in Escherichia coli. Nucleic Acids Res. 40:5569–76 [Google Scholar]
  151. Yosef I, Manor M, Kiro R, Qimron U. 2015. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria. PNAS 112:7267–72 [Google Scholar]
  152. Young JC, Dill BD, Pan C, Hettich RL, Banfield JF. et al. 2012. Phage-induced expression of CRISPR-associated proteins is revealed by shotgun proteomics in Streptococcus thermophilus. PLOS ONE 7:e38077 [Google Scholar]
  153. Zegans ME, Wagner JC, Cady KC, Murphy DM, Hammond JH, O'Toole GA. 2009. Interaction between bacteriophage DMS3 and host CRISPR region inhibits group behaviors of Pseudomonas aeruginosa. J. Bacteriol. 191:210–19 [Google Scholar]
  154. Zetsche B, Gootenberg JS, Abudayyeh OO, Slaymaker IM, Makarova KS. et al. 2015. Cpf1 is a single RNA-guided endonuclease of a class 2 CRISPR-Cas system. Cell 163:759–71 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
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