Molecular Genetics, Microbiology and Virology

, Volume 34, Issue 1, pp 16–24 | Cite as

Class 1 and 2 Integrons in Hospital Strains of Gram-Negative Bacteria Isolated in Moscow and in Regions of the Russian Federation

  • E. S. KuzinaEmail author
  • E. I. Astashkin
  • A. I. Lev
  • E. N. Ageeva
  • N. N. Kartsev
  • E. A. Svetoch
  • N. K. Fursova


Natural systems of cloning and expression of mobile gene cassettes caught by site-specific recombination, class 1 and 2 integrons, play an important role in mobilization and spread of genetic determinants of antibiotic resistance in gram-negative bacterial human pathogens, especially in a hospital environment. The gene cassettes localized in variable parts of integrons determine resistance to antibacterial drugs (AD) of different functional classes. The aim of the work is the detection and characteristic of class 1 and 2 integrons in gram-negative bacteria isolated in multidisciplinary hospitals of Moscow and other regions of the Russian Federation in 2003–2015. Clinical strains of gram-negative bacteria (n = 1248) mainly had multidrug resistance phenotype (94%). An amount of 10% of strains were resistant to AD of three functional groups; 19%, four; 42%, five; 17%, six; and 7%, seven. A high level of resistance of the studied strains to beta-lactams is associated with the presence of beta-lactamase genes of blaTEM (35% strains), blaSHV (25%), blaCTX-M (38%), blaOXA (31%), blaVIM (3%), and blaNDM (2%) types; to AD of other functional groups, with the presence of class 1 integrons (59%) and class 2 integrons (8%). Most class 1 integrons (54%) and class 2 integrons (88%) contained in its variable part 22 variants of gene cassette arrays in class 1 integrons and 4 variants in class 2 integrons. During the study, 31 types of gene cassettes were identified (including the most widespread, aadB, aacA4, aacC1, aadA1, aadA2, aadA5, blaVIM-2, dfrA1, dfrA7, dfrA12, orfC, orfE, orfY, and sat1) associated with the resistance of strains to aminoglycosides, chloramphenicol, sulfonamides, and beta-lactams, as well as orf cassettes encoding the proteins with unknown functions. New gene cassette arrays were identified: dfrA12s-orfF-aadA2 (In1249) and dfrA1-IS911-sat1-aadA1 (not numbered).


gram-negative bacteria multidrug resistance mobile genetic elements class 1 integrons class 2 integrons gene cassettes 



We are grateful to A.N. Kruglov, Cand. of Biology, senior scientist (OOO National Agency for Clinical Pharmacology and Pharmacy, Moscow); S.V. Sidorenko, Dr. of Biology, professor (Children’s Scientific and Clinical Center for Infectious Diseases, Federal Medical and Biological Agency, St. Petersburg); O.N. Ershova, Dr. of Medicine, associate professor (Burdenko National Medical Research Center for Neurosurgery, Ministry of Health, Moscow); and V.E. Malikov, Cand. of Medicine (Infectious Clinical Hospital No. 1, Moscow Healthcare Department).


This work was performed as a part of the Federal Theme of Research of the Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being “Monitoring and Study of the Properties of Causative Agents of Food and Hospital Infections, Development of Diagnostic Tools” (2016–2020).


Conflict of interests. The authors declare that they have no conflict of interest. Statement on the welfare of animals. This article does not contain any studies with animals.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in the study involving human beings complied with the ethical standards of institutional and/or national research ethics committees and the Declaration of Helsinki and its subsequent amendments or comparable ethical standards. Informed consent was obtained from each study participant.


  1. 1.
    Julia, L., Vilankar, K., Kang, H., Brown, D.E., Mathers, A., and Barnes, L.E., Environmental reservoirs of nosocomial infection: Imputation methods for linking clinical and environmental microbiological data to understand infection transmission, AMIA Annu. Symp. Proc., 2018, vol. 2017, pp. 1120–1129.Google Scholar
  2. 2.
    Antimicrobial Resistance: Global Report on Surveillance 2014, Genewa, 2014.Google Scholar
  3. 3.
    Harbarth, S., Balkhy, H.H., Goossens, H., Jarlier, V., Kluytmans, J., Laxminarayan, R., et al., Antimicrobial resistance: One world, one fight!, Antimicrob. Resist. Infect. Control, 2015, vol. 4, p. 49.CrossRefGoogle Scholar
  4. 4.
    Eidelshtein, M.V., Sukhorukova, M.V., Skleenova, E.Yu., Ivanchik, N.V., Shek, E.A., et al., Antibiotic resistance of Acinetobacter spp. nosocomial strains in Russia’s hospitals: The results of multicenter epidemiological research “MARATHON” 2013–2014, Klin. Mikrobiol. Antimikrobn. Khimioter., 2017, vol. 19, no. 1, pp. 42–48.Google Scholar
  5. 5.
    Eidelshtein, M.V., Sukhorukova, M.V., Skleenova, E.Yu., Ivanchik, N.V., Mikotina A.V., et al., Antibiotic resistance of Pseudomonas aeruginosa nosocomial strains in Russia’s hospitals: The results of multicenter epidemiological research “MARATHON” 2013–2014, Klin. Mikrobiol. Antimikrobn. Khimioter., 2017, vol. 19, no. 1, pp. 37–41.Google Scholar
  6. 6.
    Sukhorukova, M.V., Eidelshtein, M.V., Skleenova, E.Yu., Ivanchik, N.V., Mikotina A.V., et al., Antibiotic resistance of Enterobacteriaceae nosocomial strains in Russia’s hospitals: the results of multicenter epidemiological research “MARATHON” 2013–2014, Klin. Mikrobiol. Antimikrobn. Khimioter., 2017, vol. 19, no. 1, pp. 49–56.Google Scholar
  7. 7.
    Magiorakos, A.P., Srinivasan, A., Carey, R.B., Carmeli, Y., Falagas, M.E., and Giske, C.G., et al., Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance, Clin. Microbiol. Infect., 2012, vol. 18, no. 3, pp. 268–281.CrossRefGoogle Scholar
  8. 8.
    Hall, J.P.J., Brockhurst, M.A., and Harrison, E., Sampling the mobile gene pool: Innovation via horizontal gene transfer in bacteria, Philos. Trans. R. Soc. London, Ser. B, 2017, vol. 372, no. 1735, p. 20160424.Google Scholar
  9. 9.
    Tsafnat, G., Copty, J., and Partridge, S.R., RAC: Repository of antibiotic resistance cassettes, Database, 2011, bar054.Google Scholar
  10. 10.
    Michael, C.A. and Labbate, M., Gene cassette transcription in a large integron-associated array, BMC Genet., 2010, vol. 11, p. 82.CrossRefGoogle Scholar
  11. 11.
    Graham, D.W., Knapp, C.W., Christensen, B.T., McCluskey, S., and Dolfing, J., Appearance of β-lactam resistance genes in agricultural soils and clinical isolates over the 20th century, Sci. Rep., 2016, vol. 6, p. 21550.CrossRefGoogle Scholar
  12. 12.
    Wu, R.B., Alexander, T.W., Li, J.Q., Munns, K., Sharma, R., and McAllister, T.A., Prevalence and diversity of class 1 integrons and resistance genes in antimicrobial-resistant Escherichia coli originating from beef cattle administered subtherapeutic antimicrobials, J. Appl. Microbiol., 2011, vol. 111, no. 2, pp. 511–523.CrossRefGoogle Scholar
  13. 13.
    Koczura, R., Semkowska, A., and Mokracka, J., Integron-bearing Gram-negative bacteria in lake waters, Lett. Appl. Microbiol., 2014, vol. 59, no. 5, pp. 514–519.CrossRefGoogle Scholar
  14. 14.
    Deng, Y., Bao, X., Ji, L., Chen, L., Liu, J., Miao, J., et al., Resistance integrons: Class 1, 2 and 3 integrons, Ann. Clin. Microbiol. Antimicrob., 2015, vol. 14, p. 45.CrossRefGoogle Scholar
  15. 15.
    Michael, R., Gillings integrons: Past, present, and future, Microbiol. Mol. Biol. Rev., 2014, vol. 78, no. 2, p. 257.CrossRefGoogle Scholar
  16. 16.
    Partridge, S.R., Tsafnat, G., Coiera, E., and Iredell, J.R., Gene cassettes and cassette arrays in mobile resistance integrons, FEMS Microbiol. Rev., 2009, vol. 33, no. 4, pp. 757–784.CrossRefGoogle Scholar
  17. 17.
    Egorova, S., Kaftyreva, L., Grimont, P.A., and Weill, F.X., Prevalence and characterization of extended-spectrum cephalosporin-resistant nontyphoidal Salmonella isolates in adults in Saint Petersburg, Russia (2002–2005), Microb. Drug Resist., 2007, vol. 13, no. 2, pp. 102–107.CrossRefGoogle Scholar
  18. 18.
    Toleman, M.A., Vinodh, H., Sekar, U., Kamat, V., and Walsh, T.R., 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., 2007 vol. 51, no. 7, pp. 2636–2638.CrossRefGoogle Scholar
  19. 19.
    Priamchuk, S.D., Fursova, N.K., Abaev, I.V., Kovalev, Iu.N., Shishkova, N.A., Pecherskikh, E.I., et al., Genetic determinants of antibacterial resistance among nosocomial Escherichia coli, Klebsiella spp., and Enterobacter spp. isolates collected in Russia within 2003–2007, Antibiot. Khimioter., 2010, vol. 55, nos. 9–10, pp. 3–10.Google Scholar
  20. 20.
    Edelstein, M.V., Skleenova, E.N., Shevchenko, O.V., D’souza, J.W., Tapalski, D.V., et al., Spread of extensively resistant VIM-2-positive ST235 Pseudomonas aeruginosa in Belarus, Kazakhstan, and Russia: A longitudinal epidemiological and clinical study, Lancet Infect. Dis., 2013, vol. 13, no. 10, pp. 867–876.CrossRefGoogle Scholar
  21. 21.
    Solomennyi, A., Goncharov, A., and Zueva, L., Extensively drug-resistant Acinetobacter baumannii belonging to the international clonal lineage I in a Russian burn intensive care unit, Int. J. Antimicrob. Agents, 2015, vol. 45, no. 5, pp. 525–528.CrossRefGoogle Scholar
  22. 22.
    Edelstein, M., Pimkin, M., Palagin, I., Edelstein, I., and Stratchounski, L., Prevalence and molecular epidemiology of CTX-M extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae in Russian hospitals, Antimicrob. Agents Chemother., 2003, vol. 47, no. 12, pp. 3724–3732.CrossRefGoogle Scholar
  23. 23.
    Rasheed, J.K., Biddle, J.W., Anderson, K.F., Washer, L., Chenoweth, C., Perrin, J., et al., Detection of the Klebsiella pneumoniae carbapenemase type 2 Carbapenem-hydrolyzing enzyme in clinical isolates of Citrobacter freundii and K. oxytoca carrying a common plasmid, J. Clin. Microbiol., 2008, vol. 46, no. 6, pp. 2066–2069.CrossRefGoogle Scholar
  24. 24.
    Poirel, L., Carbonnelle, E., Bernabeu, S., Gutmann, L., and Rotimi, V., at al., Importation of OXA-48-producing Klebsiella pneumoniae from Kuwait, J. Antimicrob. Chemother., 2012, vol. 67, no. 8, pp. 2051–2052.CrossRefGoogle Scholar
  25. 25.
    Dallenne, C., Da Costa, A., Decre, D., Favier, C., and Arlet, G., Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae, J. Antimicrob. Chemother., 2010, vol. 65, no. 3, pp. 490–495.CrossRefGoogle Scholar
  26. 26.
    Yang, J., Chen, Y., Jia, X., Luo, Y., Song, Q., Zhao, W., et al., Dissemination and characterization of NDM-1-producing Acinetobacter pittii in an intensive care unit in China, Clin. Microbiol. Infect., 2012, vol. 18, no. 12, pp. 506–513.CrossRefGoogle Scholar
  27. 27.
    Machado, E., Cantón, R., Baquero, F., Galán, J.C., Rollán, A., et al., Integron content of extended-spectrum-beta-lactamase-producing Escherichia coli strains over 12 years in a single hospital in Madrid, Spain, Antimicrob. Agents Chemother., 2005, vol. 49, no. 5, pp. 1823–1829.CrossRefGoogle Scholar
  28. 28.
    Skurnik, M., Hyytiäinen, H.J., Happonen, L.J., Kiljunen, S., Datta, N., et al., Characterization of the genome, proteome, and structure of Yersiniophage ϕR1-37, J. Virol., 2012, vol. 86, no. 23, pp. 12625–12642.CrossRefGoogle Scholar
  29. 29.
    Jiang, X., Ni, Y., Jiang, Y., Yuan, F., Han, L., et al., Outbreak of infection caused by Enterobacter cloacae producing the novel VEB-3 beta-lactamase in China, J. Clin. Microbiol., 2005, vol. 43, no. 2, pp. 826–831.CrossRefGoogle Scholar

Copyright information

© Allerton Press, Inc. 2019

Authors and Affiliations

  • E. S. Kuzina
    • 1
    Email author
  • E. I. Astashkin
    • 1
  • A. I. Lev
    • 1
  • E. N. Ageeva
    • 1
  • N. N. Kartsev
    • 1
  • E. A. Svetoch
    • 1
  • N. K. Fursova
    • 1
  1. 1.State Research Center for Applied Microbiology and Biotechnology, Federal Service for Surveillance on Consumer Rights Protection and Human Well-BeingObolenskRussia

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