Three Novel Class 1 Integrons Detected in Multidrug-Resistant Pseudomonas aeruginosa Hospital Strains

  • E. I. Astashkin
  • A. I. Lev
  • O. N. Ershova
  • T. S. Novikova
  • E. N. Ageeva
  • G. N. Fedyukina
  • E. A. Svetoch
  • N. K. FursovaEmail author


The antibacterial resistance of healthcare-associated infection (HAI) agents is a major public health problem worldwide. Pseudomonas aeruginosa is one of the main HAI agents, especially in intensive care units (ICUs). The present study focuses on the identification of antibacterial resistance genetic determinants and on determining the structure of mobile genetic elements—novel class 1 integrons of P. aeruginosa. P. aeruginosa strains (n = 105) were collected in the Department of the Moscow Neurosurgery ICU in 2013–2016 from the respiratory system (60.0%), urine (28.6%), surgical wounds (5.7%), blood (2.9%), and cerebrospinal fluid (2.9%). The majority (92.4%) of strains were characterized by a phenotype of multidrug-resistance. Beta-lactamase genes blaVIM-2-like, which are widely distributed in Russia, were identified in 37.7% of strains. The blaCTX-M-15 gene was carried by 3.0% of strains that is the first report of such gene identification in P. aeruginosa in Russia. Class 1 integrons were detected in 63.0% of strains, with 36.7% of strains carrying seven types of gene cassette arrays: (blaVIM-2-like), (aadA6-gcuD), (aacA7-blaVIM-2-like), (aac(3 ')Ic-cmlA5), (aadA6Δ3::ISPa21e-gcuD), (gcu87-aadB-aphA15d-aadA1a), and (blaPBL-1-aacA4). The latter three gene cassette arrays are new for class 1 integrons. Identification numbers have been assigned to novel integrons: In1379, In1360, and In1375. New genetic structures were described: the aadA6 gene cassette with inserted ISPa21уe element (In1379); the gsu87 gene cassette coding hypothetical protein which is not represented in the GenBank database (In1360); novel allele of aphA15d gene cassette and the blaPBL-1 gene cassette coding new, not previously described, beta-lactamase of class A (In1375). Identification of novel genetic structures of antibacterial resistance in P. aeruginosa strains isolated in the course of 3 years indicates the activity of genetic processes associated with antibiotic resistance in hospital pathogens in the Department of Neuro-ICU, which indicates the activity of genetic processes associated with the formation of multiple drug resistance of hospital pathogens.


Pseudomonas aeruginosa novel class 1 integrons novel gene cassettes blaCTX-M-15 multidrug resistance 



This work was funded by Rospotrebnadzor.


Conflict of interests. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures for obtaining bacterial strains from patients in this study were in accordance with the “Provision of the Local Ethics Committee of the National Medical Research Center of Neurosurgery Named after Academician N.N. Burdenko of the Ministry of Health of the Russian Federation” dated November 10, 2015, and GOST (State Standard) R 523 79-2005 “Good Clinical Practice,” as well as the 1964 Helsinki Declaration of the World Medical Association as amended in 1975–2013.


  1. 1.
    Santajit, S. and Indrawattana, N., Mechanisms of antimicrobial resistance in ESKAPE pathogens, Biomed. Res. Int., 2016, vol. 2016, p. 2475067. CrossRefGoogle Scholar
  2. 2.
    Rodrigo-Troyano, A. and Sibila, O., The respiratory threat posed by multidrug resistant Gram-negative bacteria, Respirology, 2017, vol. 22, no. 7, pp. 1288–1299. CrossRefGoogle Scholar
  3. 3.
    Valadbeigi, H., Sadeghifard, N., and Salehi, M.B., The prevalence of pilA and algD virulence genes in Pseudomonas aeruginosa urinary tract and tracheal isolates, Infect. Disord.: Drug Targets, 2017, vol. 104, pp. 28–31. Google Scholar
  4. 4.
    Dortet, L., Poirel, L., and Nordmann, P., Rapid identification of carbapenemase types in Enterobacteriaceae and Pseudomonas spp. by using a biochemical test, Antimicrob. Agents Chemother., 2012, vol. 56, no. 12, pp. 6437–6440. CrossRefGoogle Scholar
  5. 5.
    Shahcheraghi, F., Badmasti, F., and Feizabadi, M.M., Molecular characterization of class1 integrons in MDR Pseudomonas aeruginosa isolated from clinical settings in Iran, Tehran, FEMS Immunol. Med. Microbiol., 2010, vol. 58, pp. 421–425.CrossRefGoogle Scholar
  6. 6.
    Terzi, H.A., Kulah, C., and Ciftci, I.H., The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa, World J. Microbiol. Biotechnol., 2014, vol. 30, pp. 2681–2687.CrossRefGoogle Scholar
  7. 7.
    Goudarzi, S.M. and Eftekhar, F., Multidrug resistance and integron carriage in clinical isolates of Pseudomonas aeruginosa in Tehran, Iran, Turk. J. Med. Sci., 2015, vol. 45, pp. 789–793.CrossRefGoogle Scholar
  8. 8.
    Chen, J., Su, Z., Liu, Y., Wang, S., Dai, X., Li, Y., et al., Identification and characterization of class p1 integrons among Pseudomonas aeruginosa isolates from patients in Zhenjiang, China, Int. J. Infect. Dis., 2009, vol. 13, pp. 717–721.CrossRefGoogle Scholar
  9. 9.
    Shamaeva, S.K., Portnyagina, U.S., Edelstein, M.V., Kuzmina, A.A., Maloguloval, S., and Varfolomeeva, N.A., Results of monitoring metallo-beta-lactamase-producing strains of Pseudomonas aeruginosa in a multi-profile hospital, Wiad. Lek., 2015, vol. 68, no. 4, pp. 546–548.Google Scholar
  10. 10.
    Miriagou, V., Cornaglia, G., Edelstein, M., Galani, I., Giske, C.G., Gniadkowski, M., et al., Acquired carbapenemases in Gram-negative bacterial pathogens: detection and surveillance issues, Clin. Microbiol. Infect., 2010, vol. 16, no. 2, pp. 112–122. CrossRefGoogle Scholar
  11. 11.
    Hong, J.S., Yoon, E.J., Lee, H., Jeong, S.H., and Lee, K., Clonal dissemination of Pseudomonas aeruginosa sequence type 235 isolates carrying blaIMP-6 and emergence of bla GES-24 and bla IMP-10 on novel genomic islands PAGI-15 and-16 in South Korea, Antimicrob. Agents Chemother., 2016, vol. 60, no. 12, pp. 7216–7223. CrossRefGoogle Scholar
  12. 12.
    al Naiemi, N., Duim, B. and Bart, A., A CTX-M extended-spectrum beta-lactamase in Pseudomonas aeruginosa and Stenotrophomonas maltophilia, J. Med. Microbiol., 2006, vol. 55, no. 11, pp. 1607–1608. CrossRefGoogle Scholar
  13. 13.
    Karim, A., Poirel, L., Nagarajan, S., and Nordmann, P., Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion sequence IS Ecp1, FEMS Microbiol. Lett., 2001, vol. 201, no. 22, pp. 237–241.Google Scholar
  14. 14.
    Priamchuk, S.D., Fursova, N.K., Abaev, I.V., Kovalev, Yu.N., Shishkova, N.A., Pecherskikh, E.I., et al., Genetic determinants of antibacterial resistance among nosocomial strains of Escherichia coli, Klebsiella spp., and Enterobacter spp. isolated in Russia for the period from 2003 up to 2007 years, Antibiot. Khimioter., 2010, vol. 55, nos. 9–10, pp. 3–10.Google Scholar
  15. 15.
    Botelho, J., Grosso, F., and Peixe, L., Characterization of the pJB12 plasmid from Pseudomonas aeruginosa reveals Tn6352, a novel putative transposon associated with mobilization of the bla VIM-2-harboring In58 Integron, Antimicrob. Agents Chemother., 2017, vol. 61, no. 5, p. e02532-16. CrossRefGoogle Scholar
  16. 16.
    Li, J., Zou, M., Dou, Q., Hu, Y., Wang, H., Yan, Q., et al., Characterization of clinical extensively drug-resistant Pseudomonas aeruginosa in the Hunan province of China, Ann. Clin. Microbiol. Antimicrob., 2016, vol. 15, no. 1, p. 35. CrossRefGoogle Scholar
  17. 17.
    Rasheed, J.K., Jay, C., Metchock, B., Berkowitz, F., Weigel, L., Crellin, J., et al., Evolution of extended-spectrum beta-lactam resistance (SHV-8) in a strain of Escherichia coli during multiple episodes of bacteremia, Antimicrob. Agents Chemother., 1997, vol. 41, no. 3, pp. 647–653.CrossRefGoogle Scholar
  18. 18.
    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
  19. 19.
    Poirel, L., Bonnin, R.A., and Nordmann, P., Genetic features of the widespread plasmid coding for the carbapenemase OXA-48, Antimicrob. Agents Chemother., 2012, vol. 56, no. 1, pp. 559–562.CrossRefGoogle Scholar
  20. 20.
    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
  21. 21.
    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, pp. 490–495.CrossRefGoogle Scholar
  22. 22.
    Jiang, X., Ni, Y., Jiang, Y., Yuan, F., Han, L., Li, M., 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
  23. 23.
    Skurnik, D., Le Menac’h, A., Zurakowski, D., Mazel, D., Courvalin, P., Denamur, E., et al., Integron-associated antibiotic resistance and phylogenetic grouping of Escherichia coli isolates from healthy subjects free of recent antibiotic exposure, Antimicrob. Agents Chemother., 2005, vol. 49, no. 7, pp. 3062–3065.CrossRefGoogle Scholar
  24. 24.
    Eckert, C., Gautier, V., and Arlet, G., DNA sequence analysis of the genetic environment of various bla CTX-M genes, J. Antimicrob. Chemother., 2006, vol. 57, no. 1, pp. 14–23. CrossRefGoogle Scholar
  25. 25.
    Feng, W., Sun, F., Wang, Q., Xiong, W., Qiu, X., Dai, X., et al., Epidemiology and resistance characteristics of Pseudomonas aeruginosa isolates from the respiratory department of a hospital in China, J. Global Antimicrob. Resist., 2017, vol. 8, pp. 142–147.CrossRefGoogle Scholar
  26. 26.
    Acharya, M., Joshi, P.R., Thapa, K., Aryal, R., Kakshapati, T., and Sharma, S., Detection of metallo-β-lactamases-encoding genes among clinical isolates of Pseudomonas aeruginosa in a tertiary care hospital, Kathmandu, Nepal, BMC Res. Notes, 2017, vol. 10, no. 1, p. 718.CrossRefGoogle Scholar
  27. 27.
    Edelstein, M.V., Skleenova, E.N., Shevchenko, O.V., D’souza, J.W., Tapalski, D.V., Azizov, I.S., 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
  28. 28.
    Fursova, N.K., Astashkin, E.I., Knyazeva, A.I., Kartsev, N.N., Leonova, E.S., Ershova, O.N., et al., The spread of bla oxa-48 and bla oxa-244 carbapenemase genes among Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter spp. isolated in Moscow: Russia, Ann. Clin. Microbiol. Antimicrob., 2015, vol. 14, p. 46. CrossRefGoogle Scholar

Copyright information

© Allerton Press, Inc. 2019

Authors and Affiliations

  • E. I. Astashkin
    • 1
  • A. I. Lev
    • 1
  • O. N. Ershova
    • 2
  • T. S. Novikova
    • 1
  • E. N. Ageeva
    • 1
  • G. N. Fedyukina
    • 1
  • E. A. Svetoch
    • 1
  • N. K. Fursova
    • 1
    Email author
  1. 1.FBIS State Research Center for Applied Microbiology and Biotechnology, RospotrebnadzorObolenskRussia
  2. 2.FSAI Burdenko National Medical Research Center of Neurosurgery, Ministry of HealthMoscowRussia

Personalised recommendations