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  • Review Article
  • Published:

Integrons: agents of bacterial evolution

Nature Reviews Microbiology volume 4, pages 608–620 (2006)Cite this article

Key Points

  • Integrons are assembly platforms that incorporate exogenous open reading frames through site-specific recombination and convert them to functional genes by ensuring their correct expression.

  • Although integrons were discovered through their involvement in the development of multiple antibiotic resistance in Gram-negative pathogens when carried in transposons, their role in genome evolution has been extended with the discovery of other, often larger, integron structures as genuine components of the genomes of many γ-proteobacterial species.

  • This Review discusses the structural differences among the different types of integron — those carried in mobile DNA elements and the chromosomal superintegrons — as well as their evolutionary history and phylogenetic relationships.

  • The different functions encoded by the integron gene cassettes are reviewed, with emphasis on those from superintegrons and other chromosomal integrons from environmental bacteria.

  • The dynamics of the intraspecies and interspecies variation of the large cassette arrays of superintegrons, and their role in the increase in antibiotic resistance, are discussed.

  • Finally, the specific recombination reactions occurring in these elements are reviewed, and a novel model involving a single-stranded substrate for recombination for cassette insertion and deletion is proposed.

Abstract

Integrons are assembly platforms — DNA elements that acquire open reading frames embedded in exogenous gene cassettes and convert them to functional genes by ensuring their correct expression. They were first identified by virtue of their important role in the spread of antibiotic-resistance genes. More recently, our understanding of their importance in bacterial genome evolution has broadened with the discovery of larger integron structures, termed superintegrons. These DNA elements contain hundreds of accessory genes and constitute a significant fraction of the genomes of many bacterial species. Here, the basic biology of integrons and superintegrons, their evolutionary history and the evidence for the existence of a novel recombination pathway is reviewed.

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Figure 1: Mobile integrons and superintegrons.
Figure 2: Phylogenetic relationship of the integron intI genes in the proteobacteria.
Figure 3: Integron recombination sites.
Figure 4: A model of integron-mediated recombination.
Figure 5: Architecture of an integrase–Vibrio cholerae repeat (VCR) synapse.

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References

  1. Mitsuhashi, S., Harada, K., Hashimoto, H. & Egawa, R. On the drug-resistance of enteric bacteria. Jpn. J. Exp. Med. 31, 47–52 (1961).

    CAS  PubMed  Google Scholar 

  2. Stokes, H. W. & Hall, R. M. A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons. Mol. Microbiol. 3, 1669–1683 (1989). This is the first description of integrons.

    CAS  PubMed  Google Scholar 

  3. Liebert, C. A., Hall, R. M. & Summers, A. O. Transposon Tn21, flagship of the floating genome. Microbiol. Mol. Biol. Rev. 63, 507–522 (1999). A comprehensive review on Tn 21 and its intricate evolution and assembly.

    CAS  PubMed Central  PubMed  Google Scholar 

  4. Hall, R. M. & Collis, C. M. Mobile gene cassettes and integrons: capture and spread of genes by site-specific recombination. Mol. Microbiol. 15, 593–600 (1995).

    CAS  PubMed  Google Scholar 

  5. Collis, C. M., Grammaticopoulos, G., Briton, J., Stokes, H. W. & Hall, R. M. Site-specific insertion of gene cassettes into integrons. Mol. Microbiol. 9, 41–52 (1993).

    CAS  PubMed  Google Scholar 

  6. Recchia, G. D. & Hall, R. M. Gene cassettes: a new class of mobile element. Microbiology 141, 3015–3027 (1995).

    CAS  PubMed  Google Scholar 

  7. Recchia, G. D. & Sherratt, D. J. in Mobile DNA II (eds Craig, N. L., Craigie, R., Gellert, M. & Lambowitz, A. M.) 162–176 (ASM Press, Washington DC, 2002).

    Google Scholar 

  8. Hall, R. M. Mobile gene cassettes and integrons: moving antibiotic resistance genes in Gram-negative bacteria. Ciba Found. Symp. 207, 192–202 (1997).

    CAS  PubMed  Google Scholar 

  9. Radstrom, P. et al. Transposon Tn5090 of plasmid R751, which carries an integron, is related to Tn7, Mu, and the retroelements. J. Bacteriol. 176, 3257–3268 (1994).

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Brown, H. J., Stokes, H. W. & Hall, R. M. The integrons In0, In2, and In5 are defective transposon derivatives. J. Bacteriol. 178, 4429–4437 (1996).

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Sundstrom, L., Roy, P. H. & Skold, O. Site-specific insertion of three structural gene cassettes in transposon Tn7. J. Bacteriol. 173, 3025–3028 (1991).

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Collis, C. M., Kim, M. J., Partridge, S. R., Stokes, H. W. & Hall, R. M. Characterization of the class 3 integron and the site-specific recombination system it determines. J. Bacteriol. 184, 3017–3026 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Shibata, N. et al. PCR typing of genetic determinants for metallo-β-lactamases and integrases carried by Gram-negative bacteria isolated in Japan, with focus on the class 3 integron. J. Clin. Microbiol. 41, 5407–5413 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Correia, M. et al. Molecular characterization of a new class 3 integron in Klebsiella pneumoniae. Antimicrob. Agents Chemother. 47, 2838–2843 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Arakawa, Y. et al. A novel integron-like element carrying the metallo-β-lactamase gene blaIMP . Antimicrob. Agents Chemother. 39, 1612–1615 (1995).

    CAS  PubMed Central  PubMed  Google Scholar 

  16. Hochhut, B. et al. Molecular analysis of antibiotic resistance gene clusters in Vibrio cholerae O139 and O1 SXT constins. Antimicrob. Agents Chemother. 45, 2991–3000 (2001).

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Rowe-Magnus, D. A. & Mazel, D. The role of integrons in antibiotic resistance gene capture. Int. J. Med. Microbiol. 292, 115–125 (2002).

    CAS  PubMed  Google Scholar 

  18. Fluit, A. C. & Schmitz, F. J. Resistance integrons and super-integrons. Clin. Microbiol. Infect. 10, 272–288 (2004).

    CAS  PubMed  Google Scholar 

  19. Biskri, L. & Mazel, D. Erythromycin esterase gene ere(A) is located in a functional gene cassette in an unusual class 2 integron. Antimicrob. Agents Chemother. 47, 3326–3331 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Ramirez, M. S., Vargas, L. J., Cagnoni, V., Tokumoto, M. & Centron, D. Class 2 integron with a novel cassette array in a Burkholderia cenocepacia isolate. Antimicrob. Agents Chemother. 49, 4418–4420 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Hansson, K., Sundstrom, L., Pelletier, A. & Roy, P. H. IntI2 integron integrase in Tn7. J. Bacteriol. 184, 1712–1721 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Collis, C. M., Recchia, G. D., Kim, M. J., Stokes, H. W. & Hall, R. M. Efficiency of recombination reactions catalyzed by class 1 integron integrase IntI1. J. Bacteriol. 183, 2535–2542 (2001). Presents a comparison of the efficiency of the different recombination reactions carried out by the class 1 integron integrase.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Nordmann, P. & Poirel, L. Emergence of plasmid-mediated resistance to quinolones in Enterobacteriaceae. J. Antimicrob. Chemother. 56, 463–469 (2005).

    CAS  PubMed  Google Scholar 

  24. Doublet, B., Weill, F. X., Fabre, L., Chaslus-Dancla, E. & Cloeckaert, A. Variant Salmonella genomic island 1 antibiotic resistance gene cluster containing a novel 3′-N-aminoglycoside acetyltransferase gene cassette, aac(3)-Id, in Salmonella enterica serovar Newport. Antimicrob. Agents Chemother. 48, 3806–3812 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Naas, T., Mikami, Y., Imai, T., Poirel, L. & Nordmann, P. Characterization of In53, a class 1 plasmid- and composite transposon-located integron of Escherichia coli which carries an unusual array of gene cassettes. J. Bacteriol. 183, 235–249 (2001).

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Nesvera, J., Hochmannova, J. & Patek, M. An integron of class 1 is present on the plasmid pCG4 from Gram-positive bacterium Corynebacterium glutamicum. FEMS Microbiol. Lett. 169, 391–395 (1998).

    CAS  PubMed  Google Scholar 

  27. Tauch, A., Gotker, S., Puhler, A., Kalinowski, J. & Thierbach, G. The 27.8-kb R-plasmid pTET3 from Corynebacterium glutamicum encodes the aminoglycoside adenyltransferase gene cassette aadA9 and the regulated tetracycline efflux system Tet 33 flanked by active copies of the widespread insertion sequence IS6100. Plasmid 48, 117–129 (2002).

    CAS  PubMed  Google Scholar 

  28. Nandi, S., Maurer, J. J., Hofacre, C. & Summers, A. O. Gram-positive bacteria are a major reservoir of class 1 antibiotic resistance integrons in poultry litter. Proc. Natl Acad. Sci. USA 101, 7118–7122 (2004). Provides evidence of the presence of integrons in various staphylococci and corynebacteria.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Barker, A., Clark, C. A. & Manning, P. A. Identification of VCR, a repeated sequence associated with a locus encoding a hemagglutinin in Vibrio cholerae O1. J. Bacteriol. 176, 5450–5458 (1994).

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Mazel, D., Dychinco, B., Webb, V. A. & Davies, J. A distinctive class of integron in the Vibrio cholerae genome. Science 280, 605–608 (1998). Describes the first superintegron and shows that integrons pre-date the use of antibiotics in medicine.

    CAS  PubMed  Google Scholar 

  31. Heidelberg, J. F. et al. DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae. Nature 406, 477–483 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Makino, K. et al. Genome sequence of Vibrio parahaemolyticus: a pathogenic mechanism distinct from that of V. cholerae. Lancet 361, 743–749 (2003).

    CAS  PubMed  Google Scholar 

  33. Chen, C. Y. et al. Comparative genome analysis of Vibrio vulnificus, a marine pathogen. Genome Res. 13, 2577–2587 (2003). Contains a comparative analysis of the cassette contents of the V. vulnificus superintegron.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Ruby, E. G. et al. Complete genome sequence of Vibrio fischeri: a symbiotic bacterium with pathogenic congeners. Proc. Natl Acad. Sci. USA 102, 3004–3009 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Vezzi, A. et al. Life at depth: Photobacterium profundum genome sequence and expression analysis. Science 307, 1459–1461 (2005).

    CAS  PubMed  Google Scholar 

  36. Vaisvila, R., Morgan, R. D., Posfai, J. & Raleigh, E. A. Discovery and distribution of super-integrons among pseudomonads. Mol. Microbiol. 42, 587–601 (2001). First description of the superintegron in pseudomonads.

    CAS  PubMed  Google Scholar 

  37. Rowe-Magnus, D. A., Guerout, A. M., Biskri, L., Bouige, P. & Mazel, D. Comparative analysis of superintegrons: engineering extensive genetic diversity in the vibrionaceae. Genome Res. 13, 428–442 (2003). First interspecies comparative analysis of the contents of superintegron cassettes.

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Rowe-Magnus, D. A. et al. The evolutionary history of chromosomal super-integrons provides an ancestry for multi-resistant integrons. Proc. Natl Acad. Sci. USA 98, 652–657 (2001). The first characterization of integrons in a large range of Vibrio species and xanthomonads, and their phylogenetic relationships.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Gillings, M. R., Holley, M. P., Stokes, H. W. & Holmes, A. J. Integrons in Xanthomonas: a source of species genome diversity. Proc. Natl Acad. Sci. USA 102, 4419–4424 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Drouin, F., Melancon, J. & Roy, P. H. The IntI-like tyrosine recombinase of Shewanella oneidensis is active as an integron integrase. J. Bacteriol. 184, 1811–1815 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Leon, G. & Roy, P. H. Excision and integration of cassettes by an integron integrase of Nitrosomonas europaea. J. Bacteriol. 185, 2036–2041 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Coleman, N., Tetu, S., Wilson, N. & Holmes, A. An unusual integron in Treponema denticola. Microbiology 150, 3524–3526 (2004).

    CAS  PubMed  Google Scholar 

  43. Nield, B. S. et al. Recovery of new integron classes from environmental DNA. FEMS Microbiol. Lett. 195, 59–65 (2001). Shows that integrons are common in environmental bacteria.

    CAS  PubMed  Google Scholar 

  44. Stokes, H. W. et al. Gene cassette PCR: sequence-independent recovery of entire genes from environmental DNA. Appl. Environ. Microbiol. 67, 5240–5246 (2001).

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Holmes, A. J. et al. The gene cassette metagenome is a basic resource for bacterial genome evolution. Environ. Microbiol. 5, 383–394 (2003).

    CAS  PubMed  Google Scholar 

  46. Nemergut, D. R., Martin, A. P. & Schmidt, S. K. Integron diversity in heavy-metal-contaminated mine tailings and inferences about integron evolution. Appl. Environ. Microbiol. 70, 1160–1168 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Rowe-Magnus, D. A. & Mazel, D. Integrons: natural tools for bacterial genome evolution. Curr. Opin. Microbiol. 4, 565–569 (2001).

    CAS  PubMed  Google Scholar 

  48. Messier, N. & Roy, P. H. Integron integrases possess a unique additional domain necessary for activity. J. Bacteriol. 183, 6699–6706 (2001). First functional analysis of the specific domain of the integron integrase.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Nunes-Duby, S. E., Kwon, H. J., Tirumalai, R. S., Ellenberger, T. & Landy, A. Similarities and differences among 105 members of the Int family of site-specific recombinases. Nucleic Acids Res. 26, 391–406 (1998).

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Rowe-Magnus, D. A., Guerout, A. -M. & Mazel, D. Super-integrons. Res. Microbiol. 150, 641–651 (1999).

    CAS  PubMed  Google Scholar 

  51. Nield, B. S. et al. New enzymes from environmental cassette arrays: functional attributes of a phosphotransferase and an RNA-methyltransferase. Protein Sci. 13, 1651–1659 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Wright, G. D. & Thompson, P. R. Aminoglycoside phosphotransferases: proteins, structure, and mechanism. Frontiers Biosci. 4, D9–D21 (1999).

    CAS  Google Scholar 

  53. Abbott, S. L. & Janda, J. M. Severe gastroenteritis associated with Vibrio hollisae infection: report of two cases and review. Clin. Infect. Dis. 18, 310–312 (1994).

    CAS  PubMed  Google Scholar 

  54. Ogawa, A. & Takeda, T. The gene encoding the heat-stable enterotoxin of Vibrio cholerae is flanked by 123-base pair direct repeats. Microbiol. Immunol. 37, 607–616 (1993).

    CAS  PubMed  Google Scholar 

  55. Barker, A. & Manning, P. A. VlpA of Vibrio cholerae O1: the first bacterial member of the α 2-microglobulin lipocalin superfamily. Microbiology 143, 1805–1813 (1997).

    CAS  PubMed  Google Scholar 

  56. Smith, A. B. & Siebeling, R. J. Identification of genetic loci required for capsular expression in Vibrio vulnificus. Infect. Immun. 71, 1091–1097 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Boucher, Y. et al. Recovery and evolutionary analysis of complete integron gene cassette arrays from Vibrio. BMC Evol. Biol. 6, 3 (2006).

    PubMed Central  PubMed  Google Scholar 

  58. Pandey, D. P. & Gerdes, K. Toxin–antitoxin loci are highly abundant in free-living but lost from host-associated prokaryotes. Nucleic Acids Res. 33, 966–976 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  59. Rowe-Magnus, D. A., Guerout, A. M. & Mazel, D. Bacterial resistance evolution by recruitment of super-integron gene cassettes. Mol. Microbiol. 43, 1657–1669 (2002).

    CAS  PubMed  Google Scholar 

  60. Yildiz, F. H., Liu, X. S., Heydorn, A. & Schoolnik, G. K. Molecular analysis of rugosity in a Vibrio cholerae O1 El Tor phase variant. Mol. Microbiol. 53, 497–515 (2004).

    CAS  PubMed  Google Scholar 

  61. Clark, C. A., Purins, L., Kaewrakon, P., Focareta, T. & Manning, P. A. The Vibrio cholerae O1 chromosomal integron. Microbiology 146, 2605–2612 (2000).

    CAS  PubMed  Google Scholar 

  62. Dziejman, M. et al. Genomic characterization of non-O1, non-O139 Vibrio cholerae reveals genes for a type III secretion system. Proc. Natl Acad. Sci. USA 102, 3465–3470 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Collis, C. M. & Hall, R. M. Gene cassettes from the insert region of integrons are excised as covalently closed circles. Mol. Microbiol. 6, 2875–2885 (1992).

    CAS  PubMed  Google Scholar 

  64. Melano, R. et al. New carbenicillin-hydrolyzing β-lactamase (CARB-7) from Vibrio cholerae non-O1, non-O139 strains encoded by the VCR region of the V. cholerae genome. Antimicrob. Agents Chemother. 46, 2162–2168 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Petroni, A. et al. CARB-9, a carbenicillinase encoded in the VCR region of Vibrio cholerae non-O1, non-O139 belongs to a family of cassette-encoded β-lactamases. Antimicrob. Agents Chemother. 48, 4042–4046 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Lim, D. et al. Insights into the molecular basis for the carbenicillinase activity of PSE-4 β-lactamase from crystallographic and kinetic studies. Biochemistry 40, 395–402 (2001).

    CAS  PubMed  Google Scholar 

  67. Tennstedt, T., Szczepanowski, R., Braun, S., Puhler, A. & Schluter, A. Occurrence of integron-associated resistance gene cassettes located on antibiotic resistance plasmids isolated from a wastewater treatment plant. FEMS Microbiol. Ecol. 45, 239–252 (2003).

    CAS  PubMed  Google Scholar 

  68. Azaro, M. A. & Landy, A. in Mobile DNA II (eds Craig, N. L., Craigie, R., Gellert, M. & Lambowitz, A. M.) 118–148 (ASM Press, Washington DC, 2002).

    Google Scholar 

  69. Martinez, E. & de la Cruz, F. Genetic elements involved in Tn21 site-specific integration, a novel mechanism for the dissemination of antibiotic resistance genes. EMBO J. 9, 1275–1281 (1990). First functional study of the integron recombination reaction, demonstrating that recombination is controlled by the encoded IntI integrase.

    CAS  PubMed Central  PubMed  Google Scholar 

  70. Francia, M. V. & Garcia Lobo, J. M. Gene integration in the Escherichia coli chromosome mediated by Tn21 integrase (Int21). J. Bacteriol. 178, 894–898 (1996).

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Francia, M. V., Avila, P., de la Cruz, F. & Garcia Lobo, J. M. A hot spot in plasmid F for site-specific recombination mediated by Tn21 integron integrase. J. Bacteriol. 179, 4419–4425 (1997).

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Recchia, G. D., Stokes, H. W. & Hall, R. M. Characterisation of specific and secondary recombination sites recognised by the integron DNA integrase. Nucleic Acids Res. 22, 2071–2078 (1994).

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Recchia, G. D. & Hall, R. M. Plasmid evolution by acquisition of mobile gene cassettes: plasmid pIE723 contains the aadB gene cassette precisely inserted at a secondary site in the IncQ plasmid RSF1010. Mol. Microbiol. 15, 179–187 (1995).

    CAS  PubMed  Google Scholar 

  74. Hansson, K., Skold, O. & Sundstrom, L. Non-palindromic attl sites of integrons are capable of site-specific recombination with one another and with secondary targets. Mol. Microbiol. 26, 441–453 (1997).

    CAS  PubMed  Google Scholar 

  75. Francia, M. V., de la Cruz, F. & Garcia Lobo, J. M. Secondary-sites for integration mediated by the Tn21 integrase. Mol. Microbiol. 10, 823–828 (1993).

    CAS  PubMed  Google Scholar 

  76. Holmes, A. J. et al. Recombination activity of a distinctive integron-gene cassette system associated with Pseudomonas stutzeri populations in soil. J. Bacteriol. 185, 918–928 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Biskri, L., Bouvier, M., Guerout, A. M., Boisnard, S. & Mazel, D. Comparative study of class 1 integron and Vibrio cholerae superintegron integrase activities. J. Bacteriol. 187, 1740–1750 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Van Duyne, G. D. in Mobile DNA II (eds Craig, N. L., Craigie, R., Gellert, M. & Lambowitz, A. M.) 93–117 (ASM Press, Washington DC, 2002).

    Google Scholar 

  79. Gravel, A., Fournier, B. & Roy, P. H. DNA complexes obtained with the integron integrase IntI1 at the attI1 site. Nucleic Acids Res. 26, 4347–4355 (1998).

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Collis, C. M., Kim, M. J., Stokes, H. W. & Hall, R. M. Binding of the purified integron DNA integrase Intl1 to integron- and cassette-associated recombination sites. Mol. Microbiol. 29, 477–490 (1998).

    CAS  PubMed  Google Scholar 

  81. Stokes, H. W., O'Gorman, D. B., Recchia, G. D., Parsekhian, M. & Hall, R. M. Structure and function of 59-base element recombination sites associated with mobile gene cassettes. Mol. Microbiol. 26, 731–745 (1997). First analysis of the structural characteristics of attC sites.

    CAS  PubMed  Google Scholar 

  82. Hall, R. M., Brookes, D. E. & Stokes, H. W. Site-specific insertion of genes into integrons: role of the 59-base element and determination of the recombination cross-over point. Mol. Microbiol. 5, 1941–1959 (1991).

    CAS  PubMed  Google Scholar 

  83. Francia, M. V., Zabala, J. C., de la Cruz, F. & Garcia-Lobo, J. M. The IntI1 integron integrase preferentially binds single-stranded DNA of the attC site. J. Bacteriol. 181, 6844–6849 (1999). Relates the discovery of the recognition of the attC site (bottom strand) by the integrase IntI1.

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Johansson, C., Kamali-Moghaddam, M. & Sundstrom, L. Integron integrase binds to bulged hairpin DNA. Nucleic Acids Res. 32, 4033–4043 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Bouvier, M., Demarre, G. & Mazel, D. Integron cassette insertion: a recombination process involving a folded single-strand substrate. EMBO J. 24, 4356–4367 (2005). In vivo demonstration of single-stranded recombination and proposal of a new recombination model involving an attC single-stranded substrate.

    CAS  PubMed Central  PubMed  Google Scholar 

  86. MacDonald, D., Demarre, G., Bouvier, M., Mazel, D. & Gopaul, D. N. Structural basis for broad DNA specificity in integron recombination. Nature 440, 1157–1162 (2006). Structural studies showing how the integrase recognizes the attC -site bottom strand and how the structural characteristics of these complexes fit the requirements of the single-stranded recombination model.

    CAS  PubMed  Google Scholar 

  87. Val, M. E. et al. The single-stranded genome of phage CTX is the form used for integration into the genome of Vibrio cholerae. Mol. Cell 19, 559–566 (2005). An example of single-strand recombination in a different system.

    CAS  PubMed  Google Scholar 

  88. Walter, A. E. et al. Coaxial stacking of helixes enhances binding of oligoribonucleotides and improves predictions of RNA folding. Proc. Natl Acad. Sci. USA 91, 9218–9222 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Work in the Mazel laboratory was supported by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS), the Programme de Recherche en Microbiologie (from the Ministère de l'Education Nationale, de l'Enseignement Supérieur et de la Recherche; MENESR), the Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER) and the European Union Collective Research on Aquaculture Biofouling (CRAB) consortium and Network of Excellence EuroPathoGenomics).

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  1. Department Génomes et Génétiqu, Unité Plasticité du Génome Bactérien- CNRS URA 2171, Institut Pasteur, 25 rue du Dr Roux, Paris, 75724, France

    Didier Mazel

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DATABASES

Entrez Genome Project

Escherichia coli

Nitrosomonas europaea

Photobacterium profundum

Proteus mirabilis

Pseudomonas stutzeri

Rhodopirellula baltica

Salmonella enterica

Shewanella oneidensis

Shigella dysenteriae

Treponema denticola

Vibrio cholerae

Vibrio fischeri

Vibrio parahaemolyticus

Vibrio salmonicida

Vibrio vulnificus

Xanthomonas campestris

FURTHER INFORMATION

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Glossary

Transposon

A mobile DNA element that can relocate within the genome of its host.

Insertion sequence

(IS) A small (<2.5 kb), generally phenotypically cryptic segment of DNA that has a simple organization and is capable of insertion at multiple sites in a target DNA molecule. Examples include IS1, IS608 and IS911.

Conjugative plasmid

A plasmid that can move from one cell to another during the process of conjugation.

SXT element

Vibrio cholerae-derived integrating and conjugative element (also referred to as a conjugative transposon or constin).

Compound transposon

A segment of DNA flanked by two similar insertion sequences, in direct or inverted orientations. Examples include Tn5 and Tn10.

Transposase

The enzyme that promotes cutting of the DNA at the ends of a transposable element and joining to the DNA molecule into which the element is to be inserted.

Transposon-mutagenesis screen

The use of transposons to generate (knock-out) mutations.

Nudix hydrolases

Nudix hydrolases (nucleoside diphosphate linked to some other moiety X) are enzymes that hydrolyse diverse nucleoside diphosphate or triphosphate derivatives.

Toxin–antitoxin families

Paired loci found in the chromosomes of almost all free-living bacteria, and many plasmids and phage genomes. They encode a toxin and its antidote, which have been shown to contribute to plasmid stability by a mechanism called post-segregational killing and are also proposed to function in bacterial programmed cell death or stress physiology.

Minimum inhibitory concentration

The lowest concentration of an antibiotic that inhibits growth of the organism.

Co-integrates

The structural fusion of replicons through a recombination reaction.

Holliday junction

A point at which the strands of two double-stranded DNA molecules exchange partners, which occurs as an intermediate in genetic recombination.

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Mazel, D. Integrons: agents of bacterial evolution. Nat Rev Microbiol 4, 608–620 (2006). https://doi.org/10.1038/nrmicro1462

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