Mobilized Integrons: Team Players in the Spread of Antibiotic Resistance Genes

  • Elena Martinez
  • Steven Djordjevic
  • H.W. Stokes
  • Piklu Roy Chowdhury


Integrons possess a site-specific recombination system and comprise a family of elements that are broadly distributed amongst the Proteobacteria. The units of capture into these elements are gene cassettes, which normally comprise of only a single gene along with an attachment site recognized by the recombination system. The class 1 integron has at least two features that distinguishes it from most other members of the integron family of integrase elements. The first of these is that they are located on mobile elements as opposed to being fixed in the chromosome and the second is that most of the associated gene cassettes include genes that encode antibiotic resistance. The linkage of the class 1 integron to mobile elements was an important step since it has meant that diverse molecular processes act cooperatively to disseminate resistance genes in Gram-negative bacteria. The selection for resistance in the antibiotic era has now led to an enormous diversity of elements that in many cases has resulted in conjugation, transposition, and site-specific recombination processes combining to spread large clusters of resistance genes. All these processes existed in nature prior to the antibiotic era but the level and extent of cooperation did not. Here we discuss how some of these complex class 1-associated mobile resistance regions evolved and their ramifications for the management of the antibiotic resistance problem.


Resistance Gene Antibiotic Resistance Hemolytic Uremic Syndrome Mobile Element Lateral Gene Transfer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Lederberg J, Tatum EL (1946) Gene recombination in Escherichia coli. Nature 158:558PubMedGoogle Scholar
  2. 2.
    Hughes VM, Datta N (1983) Conjugative plasmids in bacteria of the ‘pre-antibiotic’ era. Nature 302:725–726PubMedGoogle Scholar
  3. 3.
    Gillings MR, Stokes HW (2012) Are humans increasing bacterial evolvability? Trends Ecol Evol 27:346–352PubMedGoogle Scholar
  4. 4.
    Hall RM, Brookes DE, Stokes HW (1991) Site-specific insertion of genes into integrons: role of the 59-base element and determination of the recombination cross-over point. Mol Microbiol 5:1941–1959PubMedGoogle Scholar
  5. 5.
    Martinez E, de la Cruz F (1988) Transposon Tn21 encodes a RecA-independent site-specific integration system. Mol Gen Genet 211:320–325PubMedGoogle Scholar
  6. 6.
    Recchia GD, Hall RM (1995) Gene cassettes: a new class of mobile element. Microbiology 141:3015–3027PubMedGoogle Scholar
  7. 7.
    Stokes HW, Hall RM (1989) A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons. Mol Microbiol 3:1669–1683PubMedGoogle Scholar
  8. 8.
    Partridge SR, Tsafnat G, Coiera E, Iredell JR (2009) Gene cassettes and cassette arrays in mobile resistance integrons. FEMS Microbiol Rev 33:757–784PubMedGoogle Scholar
  9. 9.
    Holzel CS, Harms KS, Bauer J, Bauer-Unkauf I, Hormansdorfer S, Kampf P et al (2012) Diversity of antimicrobial resistance genes and class-1-integrons in phylogenetically related porcine and human Escherichia coli. Vet Microbiol 160:403–412PubMedGoogle Scholar
  10. 10.
    Maguire AJ, Brown DF, Gray JJ, Desselberger U (2001) Rapid screening technique for class 1 integrons in Enterobacteriaceae and nonfermenting gram-negative bacteria and its use in molecular epidemiology. Antimicrob Agents Chemother 45:1022–1029PubMedGoogle Scholar
  11. 11.
    Xu Z, Li L, Shi L, Shirtliff ME (2011) Class 1 integron in staphylococci. Mol Biol Rep 38:5261–5279PubMedGoogle Scholar
  12. 12.
    Brown H, Stokes H, Hall R (1996) The integrons In0, In2, and In5 are defective transposon derivatives. J Bacteriol 178:4429–4437PubMedGoogle Scholar
  13. 13.
    Kholodii GY, Mindlin SZ, Bass IA, Yurieva OV, Minakhina SV, Nikiforov VG (1995) Four genes, two ends, and a res region are involved in transposition of Tn5053: a paradigm for a novel family of transposons carrying either a mer operon or an integron. Mol Microbiol 17:1189–1200PubMedGoogle Scholar
  14. 14.
    Boucher Y, Labbate M, Koenig JE, Stokes HW (2007) Integrons: mobilizable platforms that promote genetic diversity in bacteria. Trends Microbiol 15:301–309PubMedGoogle Scholar
  15. 15.
    Mazel D (2006) Integrons: agents of bacterial evolution. Nat Rev Micro 4:608–620Google Scholar
  16. 16.
    Hansson K, Sundstrom L, Pelletier A, Roy PH (2002) IntI2 integron integrase in Tn7. J Bacteriol 184:1712–1721PubMedGoogle Scholar
  17. 17.
    Solberg OD, Ajiboye RM, Riley LW (2006) Origin of Class 1 and 2 Integrons and gene cassettes in a population-based sample of uropathogenic Escherichia coli. J Clin Microbiol 44:1347–1351PubMedGoogle Scholar
  18. 18.
    Fallah F, Karimi A, Goudarzi M, Shiva F, Navidinia M, Hadipour Jahromi M et al (2012) Jul 20) Determination of integron frequency by a polymerase chain reaction-restriction fragment length polymorphism method in multidrug-resistant Escherichia coli, which causes urinary tract infections. Microb Drug Resist 18(6):546–549PubMedGoogle Scholar
  19. 19.
    Mokracka J, Koczura R, Kaznowski A (2012) Multiresistant Enterobacteriaceae with class 1 and class 2 integrons in a municipal wastewater treatment plant. Water Res 46:3353–3363PubMedGoogle Scholar
  20. 20.
    Marquez C, Labbate M, Ingold AJ, Roy Chowdhury. P, Ramirez MS, Centron D et al (2008) Recovery of a functional class 2 integron from an Escherichia coli strain mediating a urinary tract infection. Antimicrob Agents Chemother 52:4153–4154PubMedGoogle Scholar
  21. 21.
    Barlow RS, Gobius KS (2006) Diverse class 2 integrons in bacteria from beef cattle sources. J Antimicrob Chemother 58:1133–1138PubMedGoogle Scholar
  22. 22.
    Arakawa Y, Murakami M, Suzuki K, Ito H, Wacharotayankun R, Ohsuka S et al (1995) A novel integron-like element carrying the metallo-β-lactamase gene blaIMP. Antimicrob Agents Chemother 39:1612–1615PubMedGoogle Scholar
  23. 23.
    Collis CM, Kim M-J, Partridge SR, Stokes HW, Hall RM (2002) Characterization of the class 3 integron and the site-specific recombination system it determines. J Bacteriol 184:3017–3026PubMedGoogle Scholar
  24. 24.
    Correia M, Boavida F, Grosso F, Salgado MJ, Lito LM, Cristino JM et al (2003) Molecular characterization of a new class 3 integron in Klebsiella pneumoniae. Antimicrob Agents Chemother 47:2838–2843PubMedGoogle Scholar
  25. 25.
    Shibata N, Doi Y, Yamane K, Yagi T, Kurokawa H, Shibayama K et al (2003) 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 41:5407–5413PubMedGoogle Scholar
  26. 26.
    Xu H, Davies J, Miao V (2007) Molecular characterization of class 3 integrons from Delftia spp. J Bacteriol 189:6276–6283PubMedGoogle Scholar
  27. 27.
    Cambray G, Guerout AM, Mazel D (2010) Integrons. Annu Rev Genet 44:141–166PubMedGoogle Scholar
  28. 28.
    Gillings M, Boucher Y, Labbate M, Holmes A, Krishnan S, Holley M et al (2008) The evolution of class 1 integrons and the rise of antibiotic resistance. J Bacteriol 190:5095–510044141–166PubMedGoogle Scholar
  29. 29.
    Hall RM, Brown HJ, Brookes DE, Stokes HW (1994) Integrons found in different locations have identical 5′2 ends but variable 3′2 ends. J Bacteriol 176:6286–6294PubMedGoogle Scholar
  30. 30.
    Partridge SR, Hall RM (2004) Complex multiple antibiotic and mercury resistance region derived from the r-det of NR1 (R100). Antimicrob Agents Chemother 48:4250–4255PubMedGoogle Scholar
  31. 31.
    Partridge SR, Recchia GD, Stokes HW, Hall RM (2001) Family of class 1 integrons related to In4 from Tn1696. Antimicrob Agents Chemother 45:3014–3020PubMedGoogle Scholar
  32. 32.
    Partridge SR, Brown HJ, Hall RM (2002) Characterization and movement of the class 1 integron known as Tn2521 and Tn1405. Antimicrob Agents Chemother 46:1288–1294PubMedGoogle Scholar
  33. 33.
    Levesque C, Piche L, Larose C, Roy PH (1995) PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrob Agents Chemother 39:185–191PubMedGoogle Scholar
  34. 34.
    Radstrom P, Skold O, Swedberg G, Flensburg J, Roy PH, Sundstrom L (1994) Transposon Tn5090 of plasmid R751, which carries an integron, is related to Tn7, Mu, and the retroelements. J Bacteriol 176:3257–3268PubMedGoogle Scholar
  35. 35.
    Betteridge T, Partridge SR, Iredell JR, Stokes HW (2011) Genetic context and structural diversity of class 1 integrons from human commensal bacteria in a hospital intensive care unit. Antimicrob Agents Chemother 55:3939–3943PubMedGoogle Scholar
  36. 36.
    Dawes FE, Kuzevski A, Bettelheim KA, Hornitzky MA, Djordjevic SP, Walker MJ (2012) Distribution of class 1 integrons with IS26-mediated deletions in their 3′-conserved segments in Escherichia coli of human and animal origin. PLoS One 5:e12754Google Scholar
  37. 37.
    Tato M, Coque TM, Baquero F, Canton R (2012) Dispersal of carbapenemase blaVIM-1 gene associated with different Tn402 variants, mercury transposons, and conjugative plasmids in Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother 54:320–327Google Scholar
  38. 38.
    Toleman MA, Vinodh H, Sekar U, Kamat V, Walsh TR (2007) blaVIM-2-Harboring integrons isolated in India, Russia, and the United States arise from an ancestral class 1 integron predating the formation of the 3-conserved sequence. Antimicrob Agents Chemother 51:2636–2638PubMedGoogle Scholar
  39. 39.
    Gillings MR, Labbate M, Sajjad A, Giguere NJ, Holley MP, Stokes HW (2009) Mobilization of a Tn402-like class 1 integron with a novel cassette array via flanking miniature inverted-repeat transposable element-like structures. Appl Environ Microbiol 75:6002–6004PubMedGoogle Scholar
  40. 40.
    Marquez C, Labbate M, Raymondo C, Fernandez J, Gestal AM, Holley M et al (2008) Urinary tract infections in a South American population: dynamic spread of class 1 integrons and multidrug resistance by homologous and site-specific recombination. J Clin Microbiol 46:3417–3425PubMedGoogle Scholar
  41. 41.
    Partridge SR, Brown HJ, Stokes HW, Hall RM (2001) Transposons Tn1696 and Tn21 and their integrons In4 and In2 have independent origins. Antimicrob Agents Chemother 45:1263–1270PubMedGoogle Scholar
  42. 42.
    Toleman MA, Walsh TR (2010) ISCR elements are key players in IncA/C plasmid evolution. Antimicrob Agents Chemother 54:3534PubMedGoogle Scholar
  43. 43.
    Stokes HW, Nesbo CL, Holley M, Bahl MI, Gillings MR, Boucher Y (2006) Class 1 integrons potentially predating the association with Tn402-Like transposition genes are present in a sediment microbial community. J Bacteriol 188:5722–5730PubMedGoogle Scholar
  44. 44.
    Gillings MR, Xuejun D, Hardwick SA, Holley MP, Stokes HW (2009) Gene cassettes encoding resistance to quaternary ammonium compounds: a role in the origin of clinical class 1 integrons? ISME J 3:209–215PubMedGoogle Scholar
  45. 45.
    Liebert CA, Hall RM, Summers AO (1999) Transposon Tn21, Flagship of the floating genome. Microbiol Mol Biol Rev 63:507–522PubMedGoogle Scholar
  46. 46.
    Petrova M, Gorlenko Z, Mindlin S (2011) Tn5045, a novel integron-containing antibiotic and chromate resistance transposon isolated from a permafrost bacterium. Res Microbiol 162:337–345PubMedGoogle Scholar
  47. 47.
    Allmeier H, Cresnar B, Greck M, Schmitt R (1992) Complete nucleotide sequence of Tn1721: gene organization and a novel gene product with features of a chemotaxis protein. Gene 111:11–20PubMedGoogle Scholar
  48. 48.
    Poirel L, Decousser JW, Nordmann P (2003) Insertion sequence ISEcp1B is involved in expression and mobilization of a bla(CTX-M) beta-lactamase gene. Antimicrob Agents Chemother 47:2938–2945PubMedGoogle Scholar
  49. 49.
    Yamamoto T (1989) Organization of complex transposon Tn2610 carrying two copies of tnpA and tnpR. Antimicrob Agents Chemother 33:746–750PubMedGoogle Scholar
  50. 50.
    Rogowsky P, Schmitt R (1984) Resolution of a hybrid cointegrate between transposons Tn501 and Tn1721 defines the recombination site. Mol Gen Genet 193:162–166PubMedGoogle Scholar
  51. 51.
    Zong Z, Yu R, Wang X, Lu X (2011) blaCTX-M-65 is carried by a Tn1722-like element on an IncN conjugative plasmid of ST131 Escherichia coli. J Medical Microbiol 60:435–441Google Scholar
  52. 52.
    Labbate M, Roy Chowdhury P, Stokes HW (2008) A class 1 integron present in a human commensal has a hybrid transposition module compared to Tn402: evidence of interaction with mobile DNA from natural environments. J Bacteriol 190:5318–5327PubMedGoogle Scholar
  53. 53.
    Juan C, Zamorano L, Mena A, Alberti S, Perez JL, Oliver A (2010) Metallo-β-lactamase-producing Pseudomonas putida as a reservoir of multidrug resistance elements that can be transferred to successful Pseudomonas aeruginosa clones. J Antimicrob Chemother 65:474–478PubMedGoogle Scholar
  54. 54.
    Marchiaro P, Viale AM, Ballerini V, Rossignol G, Vila AJ, Limansky A (2010) First report of a Tn402-like class 1 integron carrying blaVIM-2 in Pseudomonas putida from Argentina. J Infect Dev Ctries 4:412–416PubMedGoogle Scholar
  55. 55.
    Lagatolla C, Edalucci E, Dolzani L, Riccio ML, De Luca F, Medessi E et al (2006) Molecular evolution of metallo-β-lactamase-producing Pseudomonas aeruginosa in a nosocomial setting of high-level endemicity. J Clin Microbiol 44:2348–2353PubMedGoogle Scholar
  56. 56.
    Minakhina S, Kholodii G, Mindlin S, Yurieva O, Nikiforov V (1999) Tn5053 family transposons are res site hunters sensing plasmidal res sites occupied by cognate resolvases. Mol Microbiol 33:1059–1068PubMedGoogle Scholar
  57. 57.
    Roy Chowdhury P, Merlino J, Labbate M, Cheong EY, Gottlieb T, Stokes HW (2009) Tn6060, a transposon from a genomic island in a Pseudomonas aeruginosa clinical isolate that includes two class 1 integrons. Antimicrob Agents Chemother 53:5294–5296PubMedGoogle Scholar
  58. 58.
    Stokes HW, Elbourne LD, Hall RM (2007) Tn1403, a multiple-antibiotic resistance transposon made up of three distinct transposons. Antimicrob Agents Chemother 51:1827–1829PubMedGoogle Scholar
  59. 59.
    Martinez E, Marquez C, Ingold A, Merlino J, Djordjevic SP, Stokes HW et al (2012) Diverse mobilized class 1 integrons are common in the chromosomes of pathogenic Pseudomonas aeruginosa clinical isolates. Antimicrob. Agents Chemother 56:2169–2172Google Scholar
  60. 60.
    Roy Chowdhury P, Ingold A, Vanegas N, Martànez E, Merlino J, Merkier AK et al (2011) Dissemination of multiple drug resistance genes by class 1 integrons in Klebsiella pneumoniae isolates from four countries: a comparative study. Antimicrob Agents Chemother 55:3140–3149PubMedGoogle Scholar
  61. 61.
    Lartigue MF, Poirel L, Aubert D, Nordmann P (2006) In vitro analysis of ISEcp1B-mediated mobilization of naturally occurring beta-lactamase gene blaCTX-M of Kluyvera ascorbata. Antimicrob Agents Chemother 50:1282–1286PubMedGoogle Scholar
  62. 62.
    Olson AB, Silverman M, Boyd DA, McGeer A, Willey BM, Pong-Porter V et al (2005) Identification of a progenitor of the CTX-M-9 group of extended-spectrum β-lactamases from Kluyvera georgiana isolated in Guyana. Antimicrob Agents Chemother 49:2112–2115PubMedGoogle Scholar
  63. 63.
    Toleman MA, Bennett PM, Walsh TR (2006) ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev 70:296–316PubMedGoogle Scholar
  64. 64.
    Stokes HW, Tomaras C, Parsons Y, Hall RM (1993) The partial 3′-conserved segment duplications in the integrons In6 from pSa and In7 from pDGO100 have a common origin. Plasmid 30:39–50PubMedGoogle Scholar
  65. 65.
    Szczepanowski R, Braun S, Riedel V, Schneiker S, Krahn I, Puhler A et al (2005) The 120 592 bp IncF plasmid pRSB107 isolated from a sewage-treatment plant encodes nine different antibiotic-resistance determinants, two iron-acquisition systems and other putative virulence-associated functions. Microbiology 151:1095–1111PubMedGoogle Scholar
  66. 66.
    Daly M, Villa L, Pezzella C, Fanning S, Carattoli A (2005) Comparison of multidrug resistance gene regions between two geographically unrelated Salmonella serotypes. J Antimicrob Chemother 55:558–561PubMedGoogle Scholar
  67. 67.
    Doublet B, Praud K, Weill FX, Cloeckaert A (2009) Association of IS26-composite transposons and complex In4-type integrons generates novel multidrug resistance loci in Salmonella genomic island 1. J Antimicrob Chemother 63:282–289PubMedGoogle Scholar
  68. 68.
    Espedido BA, Partridge SR, Iredell JR (2008) bla(IMP-4) in different genetic contexts in Enterobacteriaceae isolates from Australia. Antimicrob Agents Chemother 52:2984–2987PubMedGoogle Scholar
  69. 69.
    Domingues S, Nielsen KM, da Silva GJ (2011) The blaIMP-5-carrying integron in a clinical Acinetobacter baumannii strain is flanked by miniature inverted-repeat transposable elements (MITEs). J Antimicrob Chemother 66:2667–2668PubMedGoogle Scholar
  70. 70.
    Delihas N (2008) Small mobile sequences in bacteria display diverse structure/function motifs. Mol Microbiol 67:475–481PubMedGoogle Scholar
  71. 71.
    Delihas N (2007) Enterobacterial small mobile sequences carry open reading frames and are found intragenically-evolutionary implications for formation of new peptides. Gene Regul Syst Bio 1:191–205PubMedGoogle Scholar
  72. 72.
    Venturini C, Beatson SA, Djordjevic SP, Walker MJ (2010) Multiple antibiotic resistance gene recruitment onto the enterohemorrhagic Escherichia coli virulence plasmid. FASEB J 24:1160–1166PubMedGoogle Scholar
  73. 73.
    Pan JC, Ye R, Wang HQ, Xiang HQ, Zhang W, Yu XF et al (2008) Vibrio cholerae O139 multiple-drug resistance mediated by Yersinia pestis pIP1202-like conjugative plasmids. Antimicrob Agents Chemother 52:3829–3836PubMedGoogle Scholar
  74. 74.
    Cain AK, Hall RM (2012) Evolution of a multiple antibiotic resistance region in IncHI1 plasmids: reshaping resistance regions in situ. J Antimicrob Chemother 67(12):2848–2853PubMedGoogle Scholar
  75. 75.
    Cain AK, Hall RM (2012) Evolution of IncHI2 plasmids via acquisition of transposons carrying antibiotic resistance determinants. J Antimicrob Chemother 67:1121–1127PubMedGoogle Scholar
  76. 76.
    Partridge SR, Ellem JA, Tetu SG, Zong Z, Paulsen IT, Iredell JR (2011) Complete sequence of pJIE143, a pir-type plasmid carrying ISEcp1-blaCTX-M-15 from an Escherichia coli ST131 isolate. Antimicrob Agents Chemother 55:5933–5935PubMedGoogle Scholar
  77. 77.
    Partridge SR, Paulsen IT, Iredell JR (2012) pJIE137 carrying blaCTX-M-62 is closely related to p271A carrying blaNDM-1. Antimicrob Agents Chemother 56:2166–2168PubMedGoogle Scholar
  78. 78.
    Chen YT, Liao TL, Liu YM, Lauderdale TL, Yan JJ, Tsai SF (2009) Mobilization of qnrB2 and ISCR1 in plasmids. Antimicrob Agents Chemother 53:1235–1237PubMedGoogle Scholar
  79. 79.
    Haines AS, Jones K, Batt SM, Kosheleva IA, Thomas CM (2007) Sequence of plasmid pBS228 and reconstruction of the IncP-1alpha phylogeny. Plasmid 58:76–83PubMedGoogle Scholar
  80. 80.
    Bashir A, Klammer AA, Robins WP, Chin CS, Webster D, Paxinos E et al (2012) A hybrid approach for the automated finishing of bacterial genomes. Nat Biotechnol 30(7):701–707PubMedGoogle Scholar
  81. 81.
    Hacker J, Kaper JB (2000) Pathogenicity islands and the evolution of microbes. Annu Rev Microbiol 54:641–679PubMedGoogle Scholar
  82. 82.
    Dobrindt U, Hochhut B, Hentschel U, Hacker J (2004) Genomic islands in pathogenic and environmental microorganisms. Nat Rev Micro 2:414–424Google Scholar
  83. 83.
    Fournier P-E, Vallenet D, Barbe V, Audic S, Ogata H, Poirel L et al (2006) Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet 2:e7PubMedGoogle Scholar
  84. 84.
    Lescat M, Calteau A, Hoede C, Barbe V, Touchon M, Rocha E et al (2009) A module located at a chromosomal integration hot spot is responsible for the multidrug resistance of a reference strain from Escherichia coli clonal group A. Antimicrob Agents Chemother 53:2283–2288PubMedGoogle Scholar
  85. 85.
    Klockgether J, Reva O, Larbig K, Tümmler B (2004) Sequence analysis of the mobile genome island pKLC102 of Pseudomonas aeruginosa. C J Bacteriol 186:518–534Google Scholar
  86. 86.
    Boyd D, Cloeckaert A, Chaslus-Dancla E, Mulvey MR (2002) Characterization of variant Salmonella genomic island 1 multidrug resistance regions from serovars Typhimurium DT104 and Agona. Antimicrob Agents Chemother 46:1714–1722PubMedGoogle Scholar
  87. 87.
    Klockgether J, Cramer N, Wiehlmann L, Davenport CF, Tummler B (2011) Pseudomonas aeruginosa genomic structure and diversity. Front Microbiol 2:1–18Google Scholar
  88. 88.
    Klockgether J, Wurdemann D, Reva O, Wiehlmann L, Tummler B (2006) Diversity of the abundant pKLC102/PAGI-2 family of genomic islands in Pseudomonas aeruginosa. J Bacteriol 6:2443–2459Google Scholar
  89. 89.
    Threlfall EJ, Ward LR, Frost JA, Willshaw GA (2000) The emergence and spread of antibiotic resistance in food-borne bacteria. Int J Food Microbiol 62:1–5PubMedGoogle Scholar
  90. 90.
    Zhao S, Blickenstaff K, Bodeis-Jones S, Gaines SA, Tong E, McDermott PF (2012) Comparison of the prevalences and antimicrobial resistances of Escherichia coli isolates from different retail meats in the United States, 2002 to 2008. Appl Environ Microbiol 78:1701–1707PubMedGoogle Scholar
  91. 91.
    Schwaiger K, Huther S, Holzel C, Kampf P, Bauer J (2012) Prevalence of antibiotic-resistant Enterobacteriaceae isolated from chicken and pork meat purchased at the slaughterhouse and at retail in Bavaria, Germany. Int J Food Microbiol 154:206–211PubMedGoogle Scholar
  92. 92.
    Buchholz U, Bernard H, Werber D, Bohmer MM, Remschmidt C, Wilking H et al (2011) German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med 365:1763–1770PubMedGoogle Scholar
  93. 93.
    Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, Rico A et al (2011) Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS One 6:e22751PubMedGoogle Scholar
  94. 94.
    Bielaszewska M, Mellmann A, Zhang W, Kock R, Fruth A, Bauwens A et al (2011) Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis 11:671–676PubMedGoogle Scholar
  95. 95.
    Leverstein-van Hall MA, M Blok HE, T Donders AR, Paauw A, Fluit AC, Verhoef J (2003) Multidrug resistance among Enterobacteriaceae is strongly associated with the presence of integrons and is independent of species or isolate origin. J Infect Dis 187:251–259PubMedGoogle Scholar
  96. 96.
    Doublet B, Boyd D, Mulvey MR, Cloeckaert A (2005) The Salmonella genomic island 1 is an integrative mobilizable element. Mol Microbiol 55:1911–1924PubMedGoogle Scholar
  97. 97.
    Boyd D, Peters GA, Cloeckaert A, Boumedine KS, Chaslus-Dancla E, Imberechts H et al (2001) Complete nucleotide sequence of a 43-kilobase genomic island associated with the multidrug resistance region of Salmonella enterica serovar Typhimurium DT104 and its identification in phage type DT120 and serovar Agona. J Bacteriol 183:5725–5732PubMedGoogle Scholar
  98. 98.
    Mulvey MR, Boyd DA, Olson AB, Doublet B, Cloeckaert A (2006) The genetics of Salmonella genomic island 1. Microbes Infect 8:1915–1922PubMedGoogle Scholar
  99. 99.
    Threlfall EJ (2000) Epidemic Salmonella typhimurium DT 104–a truly international multiresistant clone. J Antimicrob Chemother 46:7–10PubMedGoogle Scholar
  100. 100.
    Levings RS, Lightfoot D, Partridge SR, Hall RM, Djordjevic SP (2005) The genomic island SGI1, containing the multiple antibiotic resistance region of Salmonella enterica serovar Typhimurium DT104 or variants of it, is widely distributed in other S. enterica serovars. J Bacteriol 187:4401–4409PubMedGoogle Scholar
  101. 101.
    Evans S, Davies R (1996) Case control study of multiple-resistant Salmonella typhimurium DT104 infection of cattle in Great Britain. Vet Rec 139:557–558PubMedGoogle Scholar
  102. 102.
    Wall PG, Morgan D, Lamden K, Ryan M, Griffin M, Threlfall EJ et al (1994) A case control study of infection with an epidemic strain of multiresistant Salmonella typhimurium DT104 in England and Wales. Commun Dis Rep CDR Rev 4:R130–5PubMedGoogle Scholar
  103. 103.
    Kiss J, Nagy B, Olasz F (2012) Stability, entrapment and variant formation of Salmonella genomic island 1. PLoS One 7:e32497PubMedGoogle Scholar
  104. 104.
    Le Hello S, Weill FX, Guibert V, Praud K, Cloeckaert A, Doublet B (2012) Early multidrug-resistant Salmonella enterica Serovar Kentucky ST198 from Southeast Asia harbor Salmonella genomic island 1-J variants with a novel insertion sequence. Antimicrob Agents Chemother 56(10):5096–5102PubMedGoogle Scholar
  105. 105.
    Djordjevic SP, Cain AK, Evershed NJ, Falconer L, Levings RS, Lightfoot D et al (2009) Emergence and evolution of multiply antibiotic-resistant Salmonella enterica serovar Paratyphi B D-tartrate-utilizing strains containing SGI1. Antimicrob Agents Chemother 53:2319–2326PubMedGoogle Scholar
  106. 106.
    Levings RS, Lightfoot D, Hall RM, Djordjevic SP (2006) Aquariums as reservoirs for multidrug-resistant Salmonella Paratyphi B. Emerg Infect Dis 12:507–510PubMedGoogle Scholar
  107. 107.
    Le Hello S, Hendriksen RS, Doublet B, Fisher I, Nielsen EM, Whichard JM et al (2011) International spread of an epidemic population of Salmonella enterica serotype Kentucky ST198 resistant to ciprofloxacin. J Infect Dis 204:675–684PubMedGoogle Scholar
  108. 108.
    Levings RS, Partridge SR, Djordjevic SP, Hall RM (2007) SGI1-K, a variant of the SGI1 genomic island carrying a mercury resistance region, in Salmonella enterica serovar Kentucky. Antimicrob Agents Chemother 51:317–323PubMedGoogle Scholar
  109. 109.
    Doublet B, Butaye P, Imberechts H, Boyd D, Mulvey MR, Chaslus-Dancla E et al (2004) Salmonella genomic island 1 multidrug resistance gene clusters in Salmonella enterica serovar Agona isolated in Belgium in 1992 to 2002. Antimicrob Agents Chemother 48:2510–2517PubMedGoogle Scholar
  110. 110.
    Doublet B, Butaye P, Imberechts H, Collard JM, Chaslus-Dancla E, Cloeckaert A (2004) Salmonella agona harboring genomic island 1-A. Emerg Infect Dis 10:756–758PubMedGoogle Scholar
  111. 111.
    Cain AK, Liu X, Djordjevic SP, Hall RM (2010) Transposons related to Tn1696 in IncHI2 plasmids in multiply antibiotic resistant Salmonella enterica serovar Typhimurium from Australian animals. Microb Drug Resist 16:197–202PubMedGoogle Scholar
  112. 112.
    Johnson TJ, Lang KS (2012) IncA/C plasmids: an emerging threat to human and animal health? Mob Genet Elements 2:55–58PubMedGoogle Scholar
  113. 113.
    Fricke WF, Welch TJ, McDermott PF, Mammel MK, LeClerc JE, White DG et al (2009) Comparative genomics of the IncA/C multidrug resistance plasmid family. J Bacteriol 191:4750–4757PubMedGoogle Scholar
  114. 114.
    Lindsey RL, Fedorka-Cray PJ, Frye JG, Meinersmann RJ (2009) Inc A/C plasmids are prevalent in multidrug-resistant Salmonella enterica isolates. Appl Environ Microbiol 75:1908–1915PubMedGoogle Scholar
  115. 115.
    Allen KJ, Poppe C (2002) Occurrence and characterization of resistance to extended-spectrum cephalosporins mediated by beta-lactamase CMY-2 in Salmonella isolated from food-producing animals in Canada. Can J Vet Res 66:137–144PubMedGoogle Scholar
  116. 116.
    Garcia P, Guerra B, Bances M, Mendoza MC, Rodicio MR (2011) IncA/C plasmids mediate antimicrobial resistance linked to virulence genes in the Spanish clone of the emerging Salmonella enterica serotype 4,[5],12:i. J Antimicrob Chemother 66:543–549PubMedGoogle Scholar
  117. 117.
    Doublet B, Boyd D, Douard G, Praud K, Cloeckaert A, Mulvey MR (2012) Complete nucleotide sequence of the multidrug resistance IncA/C plasmid pR55 from Klebsiella pneumoniae isolated in 1969. J Antimicrob Chemother 67(10):2354–2360PubMedGoogle Scholar
  118. 118.
    Saidani M, Hammami S, Kammoun A, Slim A, Boutiba-Ben Boubaker I (2012) Emergence of carbapenem resistant Enterobacteriaceae producing OXA-48 carbapenemase in Tunisia. J Med Microbiol 61(Pt 12):1746–1749Google Scholar
  119. 119.
    Galimand M, Guiyoule A, Gerbaud G, Rasoamanana B, Chanteau S, Carniel E et al (1997) Multidrug resistance in Yersinia pestis mediated by a transferable plasmid. N Engl J Med 337:677–680PubMedGoogle Scholar
  120. 120.
    Pan JC, Ye R, Wang HQ, Xiang HQ, Zhang W, Yu XF et al (2008) Vibrio cholerae O139 multiple-drug resistance mediated by Yersinia pestis pIP1202-like conjugative plasmids. Antimicrob Agents Chemother 52:3829–3836PubMedGoogle Scholar
  121. 121.
    Kim MJ, Hirono I, Kurokawa K, Maki T, Hawke J, Kondo H et al (2008) Complete DNA sequence and analysis of the transferable multiple-drug resistance plasmids (R Plasmids) from Photobacterium damselae subsp. piscicida isolates collected in Japan and the United States. Antimicrob Agents Chemother 52:606–611PubMedGoogle Scholar
  122. 122.
    Reith ME, Singh RK, Curtis B, Boyd JM, Bouevitch A, Kimball J et al (2008) The genome of Aeromonas salmonicida subsp. salmonicida A449: insights into the evolution of a fish pathogen. BMC Genomics 9:427PubMedGoogle Scholar
  123. 123.
    Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R et al (2010) Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 10:597–602PubMedGoogle Scholar
  124. 124.
    Hopkins KL, Liebana E, Villa L, Batchelor M, Threlfall EJ, Carattoli A (2006) Replicon typing of plasmids carrying CTX-M or CMY beta-lactamases circulating among Salmonella and Escherichia coli isolates. Antimicrob Agents Chemother 50:3203–3206PubMedGoogle Scholar
  125. 125.
    Carattoli A, Miriagou V, Bertini A, Loli A, Colinon C, Villa L et al (2006) Replicon typing of plasmids encoding resistance to newer beta-lactams. Emerg Infect Dis 12:1145–1148.PubMedGoogle Scholar
  126. 126.
    Welch TJ, Fricke WF, McDermott PF, White DG, Rosso ML, Rasko DA et al (2007) Multiple antimicrobial resistance in plague: an emerging public health risk. PLoS One 2:e309PubMedGoogle Scholar
  127. 127.
    Switt AI, Soyer Y, Warnick LD, Wiedmann M (2009) Emergence, distribution, and molecular and phenotypic characteristics of Salmonella enterica serotype 4,5,12:i. Foodborne Pathog Dis 6:407–415PubMedGoogle Scholar
  128. 128.
    Hopkins KL, Kirchner M, Guerra B, Granier SA, Lucarelli C, Porrero MC et al (2010) Multiresistant Salmonella enterica serovar 4,[5],12:i:- in Europe: a new pandemic strain? Euro Surveill 15:19580PubMedGoogle Scholar
  129. 129.
    Lucarelli C, Dionisi AM, Torpdahl M, Villa L, Graziani C, Hopkins K et al (2010) Evidence for a second genomic island conferring multidrug resistance in a clonal group of strains of Salmonella enterica serovar Typhimurium and its monophasic variant circulating in Italy, Denmark, and the United Kingdom. J Clin Microbiol 48:2103–2109PubMedGoogle Scholar
  130. 130.
    Sarmah AK, Meyer MT, Boxall AB (2006) A global perspective on the use, sales, exposure pathways, occurrence, fate and effects of veterinary antibiotics (VAs) in the environment. Chemosphere 65:725–759PubMedGoogle Scholar
  131. 131.
    Heuer H, Schmitt H, Smalla K (2011) Antibiotic resistance gene spread due to manure application on agricultural fields. Curr Opin Microbiol 14:236–243PubMedGoogle Scholar
  132. 132.
    Heuer H, Smalla K (2007) Manure and sulfadiazine synergistically increased bacterial antibiotic resistance in soil over at least two months. Environ Microbiol 9:657–666PubMedGoogle Scholar
  133. 133.
    Binh CT, Heuer H, Gomes NC, Kotzerke A, Fulle M, Wilke BM et al (2007) Short-term effects of amoxicillin on bacterial communities in manured soil. FEMS Microbiol Ecol 62:290–302PubMedGoogle Scholar
  134. 134.
    Heuer H, Solehati Q, Zimmerling U, Kleineidam K, Schloter M, Muller T et al (2011) Accumulation of sulfonamide resistance genes in arable soils due to repeated application of manure containing sulfadiazine. Appl Environ Microbiol 77:2527–2530PubMedGoogle Scholar
  135. 135.
    Binh CT, Heuer H, Kaupenjohann M, Smalla K (2008) Piggery manure used for soil fertilization is a reservoir for transferable antibiotic resistance plasmids. FEMS Microbiol Ecol 66:25–37PubMedGoogle Scholar
  136. 136.
    Binh CT, Heuer H, Kaupenjohann M, Smalla K (2009) Diverse aadA gene cassettes on class 1 integrons introduced into soil via spread manure. Res Microbiol 160:427–433PubMedGoogle Scholar
  137. 137.
    Heuer H, Binh CT, Jechalke S, Kopmann C, Zimmerling U, Krogerrecklenfort E et al (2012) IncP-1epsilon plasmids are important vectors of antibiotic resistance genes in agricultural systems: diversification driven by class 1 integron gene cassettes. Front Microbiol 3:2PubMedGoogle Scholar
  138. 138.
    Tsafnat G, Copty J, Partridge SR. (2011) RAC: Repository of antibiotic resistance cassettes. Database : the journal of biological databases and curation. 2011:bar054.Google Scholar
  139. 139.
    Fluit AC, Schmitz FJ (1999) Class 1 integrons, gene cassettes, mobility, and epidemiology. Euro J Clin Microbiol Infect Dis 18:761–770Google Scholar
  140. 140.
    Rowe-Magnus DA, Mazel D (2002) The role of integrons in antibiotic resistance gene capture. J Med Microbiol 292:115–125Google Scholar
  141. 141.
    Fluit AC, Schmitz FJ (2004) Resistance integrons and super-integrons. Clin Microbiol Infect 10:272–288PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Elena Martinez
    • 1
  • Steven Djordjevic
    • 1
  • H.W. Stokes
    • 1
  • Piklu Roy Chowdhury
    • 1
  1. 1.The ithree instituteUniversity of Technology SydneySydneyAustralia

Personalised recommendations