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  • Review Article
  • Published:

Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow

Nature Reviews Microbiology volume 8, pages 552–563 (2010)Cite this article

Subjects

Key Points

  • Integrative and conjugative elements (ICEs) are found in a diverse array of Gram-negative and Gram-positive bacteria. ICEs are integrated into host chromosomes but can excise, circularize and transfer (through conjugation) to neighbouring cells.

  • The genes encoding key components of the ICE life cycle are often grouped into functional modules. Modules may be exchanged among ICEs as well as with other mobile elements that comprise the mobilome.

  • In addition to the core modules that mediate ICE integration, excision, conjugation and regulation, ICEs routinely encode a range of accessory functions, including virulence factors and resistance proteins for antibiotic and heavy metal resistance.

  • ICEs integrate with varying degrees of site specificity. Integrases, which mediate integration, are typically tyrosine recombinases, although there are a few cases of ICEs using a DDE transposase or a serine recombinase for this function. Integrases are also required for excision, although other factors are usually required in addition.

  • Conjugal transfer requires DNA processing, which is accomplished by a relaxase. Rolling circle replication is thought to be the primary process that liberates a single-stranded DNA molecule for transfer. The type IV secretion system seems to be the most common mechanism used by ICEs for horizontal DNA transfer.

  • There are varied and complex mechanisms that govern ICE transfer. Many ICEs encode unique factors that influence their excision and transfer frequencies.

Abstract

Integrative and conjugative elements (ICEs) are a diverse group of mobile genetic elements found in both Gram-positive and Gram-negative bacteria. These elements primarily reside in a host chromosome but retain the ability to excise and to transfer by conjugation. Although ICEs use a range of mechanisms to promote their core functions of integration, excision, transfer and regulation, there are common features that unify the group. This Review compares and contrasts the core functions for some of the well-studied ICEs and discusses them in the broader context of mobile-element and genome evolution.

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Figure 1: Schematic of a typical integrative and conjugative element life cycle.
Figure 2: Schematic of the genetic organization of SXT–R391 family integrative and conjugative elements.
Figure 3: Examples of integrative and conjugative element regulation.

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References

  1. Koonin, E. V. & Wolf, Y. I. Genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world. Nucleic Acids Res. 36, 6688–6719 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. de la Cruz, F. & Davies, J. Horizontal gene transfer and the origin of species: lessons from bacteria. Trends Microbiol. 8, 128–133 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Ochman, H., Lawrence, J. G. & Groisman, E. A. Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Gogarten, J. P., Doolittle, W. F. & Lawrence, J. G. Prokaryotic evolution in light of gene transfer. Mol. Biol. Evol. 19, 2226–2238 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Jain, R., Rivera, M. C., Moore, J. E. & Lake, J. A. Horizontal gene transfer in microbial genome evolution. Theor. Popul. Biol. 61, 489–495 (2002).

    Article  PubMed  Google Scholar 

  6. Thomas, C. M. & Nielsen, K. M. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nature Rev. Microbiol. 3, 711–721 (2005).

    Article  CAS  Google Scholar 

  7. Gogarten, J. P. & Townsend, J. P. Horizontal gene transfer, genome innovation and evolution. Nature Rev. Microbiol. 3, 679–687 (2005).

    Article  CAS  Google Scholar 

  8. Salyers, A. A., Shoemaker, N. B., Stevens, A. M. & Li, L. Y. Conjugative transposons: an unusual and diverse set of integrated gene transfer elements. Microbiol. Rev. 59, 579–590 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Osborn, A. M. & Boltner, D. When phage, plasmids, and transposons collide: genomic islands, and conjugative- and mobilizable-transposons as a mosaic continuum. Plasmid 48, 202–212 (2002).

    Article  PubMed  Google Scholar 

  10. Burrus, V. & Waldor, M. K. Shaping bacterial genomes with integrative and conjugative elements. Res. Microbiol. 155, 376–386 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Burrus, V., Marrero, J. & Waldor, M. K. The current ICE age: biology and evolution of SXT-related integrating conjugative elements. Plasmid 55, 173–183 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Burrus, V., Pavlovic, G., Decaris, B. & Guedon, G. Conjugative transposons: the tip of the iceberg. Mol. Microbiol. 46, 601–610 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Shoemaker, N. B., Barber, R. D. & Salyers, A. A. Cloning and characterization of a Bacteroides conjugal tetracycline-erythromycin resistance element by using a shuttle cosmid vector. J. Bacteriol. 171, 1294–1302 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Franke, A. E. & Clewell, D. B. Evidence for a chromosome-borne resistance transposon (Tn916) in Streptococcus faecalis that is capable of “conjugal” transfer in the absence of a conjugative plasmid. J. Bacteriol. 145, 494–502 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Waldor, M. K., Tschape, H. & Mekalanos, J. J. A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139. J. Bacteriol. 178, 4157–4165 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hochhut, B. & Waldor, M. K. Site-specific integration of the conjugal Vibrio cholerae SXT element into prfC. Mol. Microbiol. 32, 99–110 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. Ravatn, R., Studer, S., Springael, D., Zehnder, A. J. & van der Meer, J. R. Chromosomal integration, tandem amplification, and deamplification in Pseudomonas putida F1 of a 105-kilobase genetic element containing the chlorocatechol degradative genes from Pseudomonas sp. strain B13. J. Bacteriol. 180, 4360–4369 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Sullivan, J. T., Patrick, H. N., Lowther, W. L., Scott, D. B. & Ronson, C. W. Nodulating strains of Rhizobium loti arise through chromosomal symbiotic gene transfer in the environment. Proc. Natl Acad. Sci. USA 92, 8985–8989 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Brochet, M., Couve, E., Glaser, P., Guedon, G. & Payot, S. Integrative conjugative elements and related elements are major contributors to the genome diversity of Streptococcus agalactiae. J. Bacteriol. 190, 6913–6917 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nakayama, K. et al. The whole-genome sequencing of the obligate intracellular bacterium Orientia tsutsugamushi revealed massive gene amplification during reductive genome evolution. DNA Res. 15, 185–199 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Boltner, D., MacMahon, C., Pembroke, J. T., Strike, P. & Osborn, A. M. R391: a conjugative integrating mosaic comprised of phage, plasmid, and transposon elements. J. Bacteriol. 184, 5158–5169 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rice, L. B. Tn916 family conjugative transposons and dissemination of antimicrobial resistance determinants. Antimicrob. Agents Chemother. 42, 1871–1877 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Whittle, G., Shoemaker, N. B. & Salyers, A. A. The role of Bacteroides conjugative transposons in the dissemination of antibiotic resistance genes. Cell. Mol. Life Sci. 59, 2044–2054 (2002).

    Article  CAS  PubMed  Google Scholar 

  24. Davies, M. R., Shera, J., Van Domselaar, G. H., Sriprakash, K. S. & McMillan, D. J. A novel integrative conjugative element mediates genetic transfer from group G Streptococcus to other β-hemolytic streptococci. J. Bacteriol. 191, 2257–2265 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sullivan, J. T. & Ronson, C. W. Evolution of rhizobia by acquisition of a 500-kb symbiosis island that integrates into a phe-tRNA gene. Proc. Natl Acad. Sci. USA 95, 5145–5149 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. He, J. et al. The broad host range pathogen Pseudomonas aeruginosa strain PA14 carries two pathogenicity islands harboring plant and animal virulence genes. Proc. Natl Acad. Sci. USA 101, 2530–2535 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Drenkard, E. & Ausubel, F. M. Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variation. Nature 416, 740–743 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Mohd-Zain, Z. et al. Transferable antibiotic resistance elements in Haemophilus influenzae share a common evolutionary origin with a diverse family of syntenic genomic islands. J. Bacteriol. 186, 8114–8122 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Argos, P. et al. The integrase family of site-specific recombinases: regional similarities and global diversity. EMBO J. 5, 433–440 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Esposito, D. & Scocca, J. J. The integrase family of tyrosine recombinases: evolution of a conserved active site domain. Nucleic Acids Res. 25, 3605–3614 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kikuchi, Y. & Nash, H. A. Nicking-closing activity associated with bacteriophage λ int gene product. Proc. Natl Acad. Sci. USA 76, 3760–3764 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Beaber, J. W., Hochhut, B. & Waldor, M. K. Genomic and functional analyses of SXT, an integrating antibiotic resistance gene transfer element derived from Vibrio cholerae. J. Bacteriol. 184, 4259–4269 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ravatn, R., Studer, S., Zehnder, A. J. & van der Meer, J. R. Int-B13, an unusual site-specific recombinase of the bacteriophage P4 integrase family, is responsible for chromosomal insertion of the 105-kilobase clc element of Pseudomonas sp. strain B13. J. Bacteriol. 180, 5505–5514 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Ramsay, J. P., Sullivan, J. T., Stuart, G. S., Lamont, I. L. & Ronson, C. W. Excision and transfer of the Mesorhizobium loti R7A symbiosis island requires an integrase IntS, a novel recombination directionality factor RdfS, and a putative relaxase RlxS. Mol. Microbiol. 62, 723–34 (2006).

    Article  CAS  PubMed  Google Scholar 

  37. Dimopoulou, I. D., Russell, J. E., Mohd-Zain, Z., Herbert, R. & Crook, D. W. Site-specific recombination with the chromosomal tRNALeu gene by the large conjugative Haemophilus resistance plasmid. Antimicrob. Agents Chemother. 46, 1602–1603 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Qiu, X., Gurkar, A. U. & Lory, S. Interstrain transfer of the large pathogenicity island (PAPI-1) of Pseudomonas aeruginosa. Proc. Natl Acad. Sci. USA 103, 19830–19835 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Gaillard, M. et al. The clc element of Pseudomonas sp. strain B13, a genomic island with various catabolic properties. J. Bacteriol. 188, 1999–2013 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Sentchilo, V. et al. Intracellular excision and reintegration dynamics of the ICEclc genomic island of Pseudomonas knackmussii sp. strain B13. Mol. Microbiol. 72, 1293–1306 (2009).

    Article  CAS  PubMed  Google Scholar 

  41. Lee, C. A., Auchtung, J. M., Monson, R. E. & Grossman, A. D. Identification and characterization of int (integrase), xis (excisionase) and chromosomal attachment sites of the integrative and conjugative element ICEBs1 of Bacillus subtilis. Mol. Microbiol. 66, 1356–1369 (2007).

    CAS  PubMed  Google Scholar 

  42. Burrus, V. & Waldor, M. K. Control of SXT integration and excision. J. Bacteriol. 185, 5045–5054 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Scott, J. R., Bringel, F., Marra, D., Van Alstine, G. & Rudy, C. K. Conjugative transposition of Tn916: preferred targets and evidence for conjugative transfer of a single strand and for a double-stranded circular intermediate. Mol. Microbiol. 11, 1099–1108 (1994).

    Article  CAS  PubMed  Google Scholar 

  44. Lu, F. & Churchward, G. Tn916 target DNA sequences bind the C-terminal domain of integrase protein with different affinities that correlate with transposon insertion frequency. J. Bacteriol. 177, 1938–1946 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Rajeev, L., Malanowska, K. & Gardner, J. F. Challenging a paradigm: the role of DNA homology in tyrosine recombinase reactions. Microbiol. Mol. Biol. Rev. 73, 300–309 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Caparon, M. G. & Scott, J. R. Excision and insertion of the conjugative transposon Tn916 involves a novel recombination mechanism. Cell 59, 1027–1034 (1989).

    Article  CAS  PubMed  Google Scholar 

  47. Taylor, K. L. & Churchward, G. Specific DNA cleavage mediated by the integrase of conjugative transposon Tn916. J. Bacteriol. 179, 1117–1125 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cheng, Q., Paszkiet, B. J., Shoemaker, N. B., Gardner, J. F. & Salyers, A. A. Integration and excision of a Bacteroides conjugative transposon, CTnDOT. J. Bacteriol. 182, 4035–4043 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Malanowska, K., Salyers, A. A. & Gardner, J. F. Characterization of a conjugative transposon integrase, IntDOT. Mol. Microbiol. 60, 1228–1240 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Bedzyk, L. A., Shoemaker, N. B., Young, K. E. & Salyers, A. A. Insertion and excision of Bacteroides conjugative chromosomal elements. J. Bacteriol. 174, 166–172 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Haren, L., Ton-Hoang, B. & Chandler, M. Integrating DNA: transposases and retroviral integrases. Annu. Rev. Microbiol. 53, 245–281 (1999).

    Article  CAS  PubMed  Google Scholar 

  52. Brochet, M. et al. Atypical association of DDE transposition with conjugation specifies a new family of mobile elements. Mol. Microbiol. 71, 948–959 (2009).

    Article  CAS  PubMed  Google Scholar 

  53. Wang, H. & Mullany, P. The large resolvase TndX is required and sufficient for integration and excision of derivatives of the novel conjugative transposon Tn5397. J. Bacteriol. 182, 6577–6583 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Mullany, P. et al. Genetic analysis of a tetracycline resistance element from Clostridium difficile and its conjugal transfer to and from Bacillus subtilis. J. Gen. Microbiol. 136, 1343–1349 (1990).

    Article  CAS  PubMed  Google Scholar 

  55. Mullany, P., Pallen, M., Wilks, M., Stephen, J. R. & Tabaqchali, S. A group II intron in a conjugative transposon from the Gram-positive bacterium, Clostridium difficile. Gene 174, 145–150 (1996).

    Article  CAS  PubMed  Google Scholar 

  56. Lewis, J. A. & Hatfull, G. F. Control of directionality in integrase-mediated recombination: examination of recombination directionality factors (RDFs) including Xis and Cox proteins. Nucleic Acids Res. 29, 2205–2216 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Marra, D. & Scott, J. R. Regulation of excision of the conjugative transposon Tn916. Mol. Microbiol. 31, 609–621 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. Hinerfeld, D. & Churchward, G. Xis protein of the conjugative transposon Tn916 plays dual opposing roles in transposon excision. Mol. Microbiol. 41, 1459–1467 (2001).

    Article  CAS  PubMed  Google Scholar 

  59. Rudy, C. K., Scott, J. R. & Churchward, G. DNA binding by the Xis protein of the conjugative transposon Tn916. J. Bacteriol. 179, 2567–2572 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Connolly, K. M., Iwahara, M. & Clubb, R. T. Xis protein binding to the left arm stimulates excision of conjugative transposon Tn916. J. Bacteriol. 184, 2088–2099 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Scott, J. R., Kirchman, P. A. & Caparon, M. G. An intermediate in transposition of the conjugative transposon Tn916. Proc. Natl Acad. Sci. USA 85, 4809–4813 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Sutanto, Y., Shoemaker, N. B., Gardner, J. F. & Salyers, A. A. Characterization of Exc, a novel protein required for the excision of Bacteroides conjugative transposon. Mol. Microbiol. 46, 1239–1246 (2002).

    Article  CAS  PubMed  Google Scholar 

  63. Cheng, Q., Sutanto, Y., Shoemaker, N. B., Gardner, J. F. & Salyers, A. A. Identification of genes required for excision of CTnDOT, a Bacteroides conjugative transposon. Mol. Microbiol. 41, 625–632 (2001).

    Article  CAS  PubMed  Google Scholar 

  64. Minoia, M. et al. Stochasticity and bistability in horizontal transfer control of a genomic island in Pseudomonas. Proc. Natl Acad. Sci. USA 105, 20792–20797 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Lee, C. A., Babic, A. & Grossman, A. D. Autonomous plasmid-like replication of a conjugative transposon. Mol. Microbiol. 75, 268–279 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lee, P. S. & Grossman, A. D. The chromosome partitioning proteins Soj (ParA) and Spo0J (ParB) contribute to accurate chromosome partitioning, separation of replicated sister origins, and regulation of replication initiation in Bacillus subtilis. Mol. Microbiol. 60, 853–869 (2006).

    Article  CAS  PubMed  Google Scholar 

  67. Moller-Jensen, J., Jensen, R. B. & Gerdes, K. Plasmid and chromosome segregation in prokaryotes. Trends Microbiol. 8, 313–320 (2000).

    Article  CAS  PubMed  Google Scholar 

  68. Klockgether, J., Reva, O., Larbig, K. & Tummler, B. Sequence analysis of the mobile genome island pKLC102 of Pseudomonas aeruginosa C. J. Bacteriol. 186, 518–534 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Van Melderen, L. & Saavedra De Bast, M. Bacterial toxin-antitoxin systems: more than selfish entities? PLoS Genet. 5, e1000437 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Magnuson, R. D. Hypothetical functions of toxin-antitoxin systems. J. Bacteriol. 189, 6089–6092 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  72. Wozniak, R. A. & Waldor, M. K. A toxin-antitoxin system promotes the maintenance of an integrative conjugative element. PLoS Genet. 5, e1000439 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Lanka, E. & Wilkins, B. M. DNA processing reactions in bacterial conjugation. Annu. Rev. Biochem. 64, 141–169 (1995).

    Article  CAS  PubMed  Google Scholar 

  74. Hamilton, C. M. et al. TraG from RP4 and TraG and VirD4 from Ti plasmids confer relaxosome specificity to the conjugal transfer system of pTiC58. J. Bacteriol. 182, 1541–1548 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Llosa, M., Gomis- Rüth, F. X., Coll, M. & de la Cruz, F. Bacterial conjugation: a two-step mechanism for DNA transport. Mol. Microbiol. 45, 1–8 (2002).

    Article  CAS  PubMed  Google Scholar 

  76. Lee, C. A. & Grossman, A. D. Identification of the origin of transfer (oriT) and DNA relaxase required for conjugation of the integrative and conjugative element ICEBs1 of Bacillus subtilis. J. Bacteriol. 189, 7254–7261 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Jaworski, D. D. & Clewell, D. B. A functional origin of transfer (oriT) on the conjugative transposon Tn916. J. Bacteriol. 177, 6644–6651 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Rocco, J. M. & Churchward, G. The integrase of the conjugative transposon Tn916 directs strand- and sequence-specific cleavage of the origin of conjugal transfer, oriT, by the endonuclease Orf20. J. Bacteriol. 188, 2207–2213 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ceccarelli, D., Daccord, A., Rene, M. & Burrus, V. Identification of the origin of transfer (oriT) and a new gene required for mobilization of the SXT/R391 family of integrating conjugative elements. J. Bacteriol. 190, 5328–5338 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Possoz, C., Ribard, C., Gagnat, J., Pernodet, J. L. & Guerineau, M. The integrative element pSAM2 from Streptomyces: kinetics and mode of conjugal transfer. Mol. Microbiol. 42, 159–166 (2001).

    Article  CAS  PubMed  Google Scholar 

  81. Hagege, J., Pernodet, J. L., Friedmann, A. & Guerineau, M. Mode and origin of replication of pSAM2, a conjugative integrating element of Streptomyces ambofaciens. Mol. Microbiol. 10, 799–812 (1993).

    Article  CAS  PubMed  Google Scholar 

  82. Dimopoulou, I. D., Jordens, J. Z., Legakis, N. J. & Crook, D. W. A molecular analysis of Greek and UK Haemophilus influenzae conjugative resistance plasmids. J. Antimicrob. Chemother. 39, 303–307 (1997).

    Article  CAS  PubMed  Google Scholar 

  83. Leaves, N. I. et al. Epidemiological studies of large resistance plasmids in Haemophilus. J. Antimicrob. Chemother. 45, 599–604 (2000).

    Article  CAS  PubMed  Google Scholar 

  84. Christie, P. J., Atmakuri, K., Krishnamoorthy, V., Jakubowski, S. & Cascales, E. Biogenesis, architecture, and function of bacterial type IV secretion systems. Annu. Rev. Microbiol. 59, 451–485 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Cascales, E. & Christie, P. J. The versatile bacterial type IV secretion systems. Nature Rev. Microbiol. 1, 137–149 (2003).

    Article  CAS  Google Scholar 

  86. Fricke, W. F. et al. Comparative genomics of the IncA/C multidrug resistance plasmid family. J. Bacteriol. 191, 4750–4757 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wozniak, R. A. et al. Comparative ICE genomics: insights into the evolution of the SXT/R391 family of ICEs. PLoS Genet. 5, e1000786 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Berkmen, M. B., Lee, C. A., Loveday, E. K. & Grossman, A. D. Polar positioning of a conjugation protein from the integrative and conjugative element ICEBs1 of Bacillus subtilis. J. Bacteriol. 192, 38–45 (2009).

    Article  PubMed Central  CAS  Google Scholar 

  89. Christie, P. J. & Vogel, J. P. Bacterial type IV secretion: conjugation systems adapted to deliver effector molecules to host cells. Trends Microbiol. 8, 354–360 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Juhas, M. et al. Novel type IV secretion system involved in propagation of genomic islands. J. Bacteriol. 189, 761–771 (2007).

    Article  CAS  PubMed  Google Scholar 

  91. Juhas, M. et al. Sequence and functional analyses of Haemophilus spp. genomic islands. Genome Biol. 8, R237 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Sullivan, J. T. et al. Comparative sequence analysis of the symbiosis island of Mesorhizobium loti strain R7A. J. Bacteriol. 184, 3086–3095 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Hubber, A., Vergunst, A. C., Sullivan, J. T., Hooykaas, P. J. & Ronson, C. W. Symbiotic phenotypes and translocated effector proteins of the Mesorhizobium loti strain R7A VirB/D4 type IV secretion system. Mol. Microbiol. 54, 561–574 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Hagege, J. et al. Transfer functions of the conjugative integrating element pSAM2 from Streptomyces ambofaciens: characterization of a kil-kor system associated with transfer. J. Bacteriol. 175, 5529–5538 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. te Poele, E. M., Bolhuis, H. & Dijkhuizen, L. Actinomycete integrative and conjugative elements. Antonie Van Leeuwenhoek 94, 127–143 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Reuther, J., Gekeler, C., Tiffert, Y., Wohlleben, W. & Muth, G. Unique conjugation mechanism in mycelial streptomycetes: a DNA-binding ATPase translocates unprocessed plasmid DNA at the hyphal tip. Mol. Microbiol. 61, 436–446 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Marrero, J. & Waldor, M. K. The SXT/R391 family of integrative conjugative elements is composed of two exclusion groups. J. Bacteriol. 189, 3302–3305 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Marrero, J. & Waldor, M. K. Interactions between inner membrane proteins in donor and recipient cells limit conjugal DNA transfer. Dev. Cell 8, 963–970 (2005).

    Article  CAS  PubMed  Google Scholar 

  99. Marrero, J. & Waldor, M. K. Determinants of entry exclusion within Eex and TraG are cytoplasmic. J. Bacteriol. 189, 6469–6473 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Hochhut, B., Beaber, J. W., Woodgate, R. & Waldor, M. K. Formation of chromosomal tandem arrays of the SXT element and R391, two conjugative chromosomally integrating elements that share an attachment site. J. Bacteriol. 183, 1124–1132 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Burrus, V. & Waldor, M. K. Formation of SXT tandem arrays and SXT-R391 hybrids. J. Bacteriol. 186, 2636–2645 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Oppenheim, A. B., Kobiler, O., Stavans, J., Court, D. L. & Adhya, S. Switches in bacteriophage lambda development. Annu. Rev. Genet. 39, 409–429 (2005).

    Article  CAS  PubMed  Google Scholar 

  103. Auchtung, J. M., Lee, C. A., Garrison, K. L. & Grossman, A. D. Identification and characterization of the immunity repressor (ImmR) that controls the mobile genetic element ICEBs1 of Bacillus subtilis. Mol. Microbiol. 64, 1515–1528 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Possoz, C., Gagnat, J., Sezonov, G., Guerineau, M. & Pernodet, J. L. Conjugal immunity of Streptomyces strains carrying the integrative element pSAM2 is due to the pif gene (pSAM2 immunity factor). Mol. Microbiol. 47, 1385–1393 (2003).

    Article  CAS  PubMed  Google Scholar 

  105. Roberts, A. P. & Mullany, P. A modular master on the move: the Tn916 family of mobile genetic elements. Trends Microbiol. 17, 251–258 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Ravatn, R., Zehnder, A. J. & van der Meer, J. R. Low-frequency horizontal transfer of an element containing the chlorocatechol degradation genes from Pseudomonas sp. strain B13 to Pseudomonas putida F1 and to indigenous bacteria in laboratory-scale activated-sludge microcosms. Appl. Environ. Microbiol. 64, 2126–2132 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Springael, D. et al. Community shifts in a seeded 3-chlorobenzoate degrading membrane biofilm reactor: indications for involvement of in situ horizontal transfer of the clc-element from inoculum to contaminant bacteria. Environ. Microbiol. 4, 70–80 (2002).

    Article  CAS  PubMed  Google Scholar 

  108. Auchtung, J. M., Lee, C. A., Monson, R. E., Lehman, A. P. & Grossman, A. D. Regulation of a Bacillus subtilis mobile genetic element by intercellular signaling and the global DNA damage response. Proc. Natl Acad. Sci. USA 102, 12554–12559 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Serfiotis-Mitsa, D. et al. The Orf18 gene product from conjugative transposon Tn916 is an ArdA antirestriction protein that inhibits type I DNA restriction-modification systems. J. Mol. Biol. 383, 970–981 (2008).

    Article  CAS  PubMed  Google Scholar 

  110. Beaber, J. W. & Waldor, M. K. Identification of operators and promoters that control SXT conjugative transfer. J. Bacteriol. 186, 5945–5949 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Beaber, J. W., Hochhut, B. & Waldor, M. K. SOS response promotes horizontal dissemination of antibiotic resistance genes. Nature 427, 72–74 (2004).

    Article  CAS  PubMed  Google Scholar 

  112. Ptashne, M. A Genetic Switch: Phage Lambda Revisited (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, 2004).

    Google Scholar 

  113. Bose, B., Auchtung, J. M., Lee, C. A. & Grossman, A. D. A conserved anti-repressor controls horizontal gene transfer by proteolysis. Mol. Microbiol. 70, 570–582 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Ramsay, J. P. et al. A LuxRI-family regulatory system controls excision and transfer of the Mesorhizobium loti strain R7A symbiosis island by activating expression of two conserved hypothetical genes. Mol. Microbiol. 73, 1141–1155 (2009).

    Article  CAS  PubMed  Google Scholar 

  115. Stevens, A. M., Shoemaker, N. B. & Salyers, A. A. The region of a Bacteroides conjugal chromosomal tetracycline resistance element which is responsible for production of plasmidlike forms from unlinked chromosomal DNA might also be involved in transfer of the element. J. Bacteriol. 172, 4271–4279 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Moon, K., Shoemaker, N. B., Gardner, J. F. & Salyers, A. A. Regulation of excision genes of the Bacteroides conjugative transposon CTnDOT. J. Bacteriol. 187, 5732–5741 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Whittle, G., Shoemaker, N. B. & Salyers, A. A. Characterization of genes involved in modulation of conjugal transfer of the Bacteroides conjugative transposon CTnDOT. J. Bacteriol. 184, 3839–3847 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Wang, Y., Shoemaker, N. B. & Salyers, A. A. Regulation of a Bacteroides operon that controls excision and transfer of the conjugative transposon CTnDOT. J. Bacteriol. 186, 2548–2557 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Wang, Y., Rotman, E. R., Shoemaker, N. B. & Salyers, A. A. Translational control of tetracycline resistance and conjugation in the Bacteroides conjugative transposon CTnDOT. J. Bacteriol. 187, 2673–2680 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Jeters, R. T., Wang, G. R., Moon, K., Shoemaker, N. B. & Salyers, A. A. Tetracycline-associated transcriptional regulation of transfer genes of the Bacteroides conjugative transposon CTnDOT. J. Bacteriol. 191, 6374–6382 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Celli, J., Poyart, C. & Trieu-Cuot, P. Use of an excision reporter plasmid to study the intracellular mobility of the conjugative transposon Tn916 in Gram-positive bacteria. Microbiol. 143, 1253–1261 (1997).

    Article  CAS  Google Scholar 

  122. Celli, J. & Trieu-Cuot, P. Circularization of Tn916 is required for expression of the transposon-encoded transfer functions: characterization of long tetracycline-inducible transcripts reading through the attachment site. Mol. Microbiol. 28, 103–117 (1998).

    Article  CAS  PubMed  Google Scholar 

  123. Su, Y. A., He, P. & Clewell, D. B. Characterization of the tet(M) determinant of Tn916: evidence for regulation by transcription attenuation. Antimicrob. Agents Chemother. 36, 769–778 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sentchilo, V., Zehnder, A. J. & van der Meer, J. R. Characterization of two alternative promoters for integrase expression in the clc genomic island of Pseudomonas sp. strain B13. Mol. Microbiol. 49, 93–104 (2003).

    Article  CAS  PubMed  Google Scholar 

  125. Sentchilo, V., Ravatn, R., Werlen, C., Zehnder, A. J. & van der Meer, J. R. Unusual integrase gene expression on the clc genomic island in Pseudomonas sp. strain B13. J. Bacteriol. 185, 4530–4538 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Sezonov, G., Duchene, A. M., Friedmann, A., Guerineau, M. & Pernodet, J. L. Replicase, excisionase, and integrase genes of the Streptomyces element pSAM2 constitute an operon positively regulated by the pra gene. J. Bacteriol. 180, 3056–3061 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Sezonov, G., Possoz, C., Friedmann, A., Pernodet, J. L. & Guerineau, M. KorSA from the Streptomyces integrative element pSAM2 is a central transcriptional repressor: target genes and binding sites. J. Bacteriol. 182, 1243–1250 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Susanna, K. A., den Hengst, C. D., Hamoen, L. W. & Kuipers, O. P. Expression of transcription activator ComK of Bacillus subtilis in the heterologous host Lactococcus lactis leads to a genome-wide repression pattern: a case study of horizontal gene transfer. Appl. Environ. Microbiol. 72, 404–411 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Nguyen, T. N., Phan, Q. G., Duong, L. P., Bertrand, K. P. & Lenski, R. E. Effects of carriage and expression of the Tn10 tetracycline-resistance operon on the fitness of Escherichia coli K12. Mol. Biol. Evol. 6, 213–225 (1989).

    CAS  PubMed  Google Scholar 

  130. Lenski, R. E. et al. Epistatic effects of promoter and repressor functions of the Tn10 tetracycline-resistance operon of the fitness of Escherichia coli. Mol. Ecol. 3, 127–135 (1994).

    Article  CAS  PubMed  Google Scholar 

  131. Dahlberg, C. & Chao, L. Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12. Genetics 165, 1641–1649 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Doyle, M. et al. An H-NS-like stealth protein aids horizontal DNA transmission in bacteria. Science 315, 251–252 (2007).

    Article  CAS  PubMed  Google Scholar 

  133. Moon, K., Sonnenburg, J. & Salyers, A. A. Unexpected effect of a Bacteroides conjugative transposon, CTnDOT, on chromosomal gene expression in its bacterial host. Mol. Microbiol. 64, 1562–1571 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Gaillard, M., Pernet, N., Vogne, C., Hagenbuchle, O. & van der Meer, J. R. Host and invader impact of transfer of the clc genomic island into Pseudomonas aeruginosa PAO1. Proc. Natl Acad. Sci. USA 105, 7058–7063 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Cavalli, L. L., Lederberg, J. & Lederberg, E. M. An infective factor controlling sex compatibility in Bacterium coli. J. Gen. Microbiol. 8, 89–103 (1953).

    CAS  PubMed  Google Scholar 

  136. Babic, A., Lindner, A. B., Vulic, M., Stewart, E. J. & Radman, M. Direct visualization of horizontal gene transfer. Science 319, 1533–1536 (2008).

    Article  CAS  PubMed  Google Scholar 

  137. Hochhut, B., Marrero, J. & Waldor, M. K. Mobilization of plasmids and chromosomal DNA mediated by the SXT element, a constin found in Vibrio cholerae O139. J. Bacteriol. 182, 2043–2047 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Osorio, C. R. et al. Genomic and functional analysis of ICEPdaSpa1, a fish-pathogen-derived SXT-related integrating conjugative element that can mobilize a virulence plasmid. J. Bacteriol. 190, 3353–3361 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Flannagan, S. E. & Clewell, D. B. Conjugative transfer of Tn916 in Enterococcus faecalis: trans activation of homologous transposons. J. Bacteriol. 173, 7136–7141 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Pavlovic, G., Burrus, V., Gintz, B., Decaris, B. & Guedon, G. Evolution of genomic islands by deletion and tandem accretion by site-specific recombination: ICESt1-related elements from Streptococcus thermophilus. Microbiology 150, 759–774 (2004).

    Article  CAS  PubMed  Google Scholar 

  141. Garriss, G., Waldor, M. K. & Burrus, V. Mobile antibiotic resistance encoding elements promote their own diversity. PLoS Genet. 5, e1000775 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

Our work on ICEs is supported by the US National Institute of Allergy and Infectious Diseases (grant R37 AI-42347) and the Howard Hughes Medical Institute. We thank B. Davis and A. Mandlik for comments on the manuscript and previous laboratory members B. Hochhut, J. Beaber, V. Burrus and J. Marrero, who all contributed to our studies of ICEs.

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Authors and Affiliations

  1. Program in Genetics, Tufts University, Boston, 02111, Massachusetts, USA

    Rachel A. F. Wozniak

  2. Brigham and Women's Hospital, Channing Laboratory and Howard Hughes Medical Institute, Harvard Medical School, 181 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Matthew K. Waldor

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Correspondence to Matthew K. Waldor.

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DATABASES

Entrez Genome Project

Bacillus anthracis

Bacillus subtilis

Bacteriodes thetaiotaomicron

Clostridium difficile

Enterococcus faecalis

Haemophilus influenzae

Listeria monocytogenes

Orientia tsutsugamushi

Pseudomonas aeruginosa

Shigella flexneri

Streptococcus agalactiae

Streptomyces ambofaciens

Vibrio cholerae

FURTHER INFORMATION

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Glossary

Conjugation

Direct transfer of genetic material between two bacteria.

Transduction

Bacteriophage-mediated DNA transfer.

Transformation

The uptake of exogenous DNA from the environment.

Integrative and conjugative element

A chromosomal element that can be excised and transferred to another cell.

Hfr-like transfer

Transfer of adjacent chromosomal DNA by an integrated plasmid

Toxin–antitoxin pair

A system in which an unstable antitoxin prevents the action of a stable toxin. When the genes encoding this system are lost, the antitoxin is lost and the cell is killed by the toxin.

Bistable

Regulated in a manner that can result in one of two distinct states.

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Wozniak, R., Waldor, M. Integrative and conjugative elements: mosaic mobile genetic elements enabling dynamic lateral gene flow. Nat Rev Microbiol 8, 552–563 (2010). https://doi.org/10.1038/nrmicro2382

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