1887

Abstract

Molecular detection and surveillance of the resistance genes harboured by are becoming increasingly important in assessing and controlling spread and colonization in hospitals, and in guiding the treatment of infections. This study analysed the resistance mechanisms of carbapenem-resistant clinical isolates of and identified the associated integron-borne metallo--lactamase (MBL)-encoding genes. Twenty-seven imipenem (IPM)-resistant clinical isolates of were divided into three groups according to their resistance levels to carbapenems. Strains bearing showed extremely high-level resistance to IPM, with MICs of 512–2048 μg ml. By comparison, strains bearing , and showed an intermediate level of resistance, with MICs of 32–256 μg ml. The non-MBL-producing strains showed a low level of resistance, with MICs of 8–32 μg ml. The same trend in resistance levels was also observed when resistance to other carbapenems, such as meropenem and panipenem, was determined. DNA sequencing showed that the MBL-encoding gene cassettes were carried by class 1 integrons. The , and gene cassettes were preceded by a hybrid promoter, TGGACA-N-TAAACT, and the gene cassette was preceded by a weak promoter, TGGACA-N-TAAGCT. Most of the MBL-encoding genes were linked to one or two resistance genes encoding aminoglycoside-modifying enzymes, such as , , , , , and , highlighting the multidrug-resistant properties of these clinical isolates.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.010017-0
2009-08-01
2019-09-21
Loading full text...

Full text loading...

/deliver/fulltext/jmm/58/8/1080.html?itemId=/content/journal/jmm/10.1099/jmm.0.010017-0&mimeType=html&fmt=ahah

References

  1. Arakawa, Y., Shibata, N., Shibayama, K., Kurokawa, H., Yagi, T., Fujiwara, H. & Goto, M. ( 2000; ). Convenient test for screening metallo-β-lactamase-producing Gram-negative bacteria by using thiol compounds. J Clin Microbiol 38, 40–43.
    [Google Scholar]
  2. Bennett, P. M. ( 1999; ). Integrons and gene cassettes: a genetic construction kit for bacteria. J Antimicrob Chemother 43, 1–4.
    [Google Scholar]
  3. Bunny, K. L., Hall, R. M. & Stokes, H. W. ( 1995; ). New mobile gene cassettes containing an aminoglycoside resistance gene, aacA7, and a chloramphenicol resistance gene, catB3, in an integron in pBWH301. Antimicrob Agents Chemother 39, 686–693.[CrossRef]
    [Google Scholar]
  4. Bush, K. ( 1998; ). Metallo-β-lactamases: a class apart. Clin Infect Dis 27 (Suppl. 1), S48–S53.[CrossRef]
    [Google Scholar]
  5. Collis, C. M. & Hall, R. M. ( 1995; ). Expression of antibiotic resistance genes in the integrated cassettes of integrons. Antimicrob Agents Chemother 39, 155–162.[CrossRef]
    [Google Scholar]
  6. Gibb, A. P., Tribuddharat, C., Moore, R. A., Louie, T. J., Krulicki, W., Livermore, D. M., Palepou, M. F. & Woodford, N. ( 2002; ). Nosocomial outbreak of carbapenem-resistant Pseudomonas aeruginosa with a new bla IMP allele, bla IMP-7. Antimicrob Agents Chemother 46, 255–258.[CrossRef]
    [Google Scholar]
  7. Gilbert, D. N., Moellering, R. C., Eliopoulos, G. M. & Sande, M. A. ( 2005; ). The Sanford Guide to Antimicrobial Therapy 2005, 35th edn. Hyde Park, VT: Antimicrobial Therapy.
  8. Hu, Z. & Zhao, W.-H. ( 2009; ). Identification of plasmid- and integron-borne bla IMP-1 and bla IMP-10 in clinical isolates of Serratia marcescens. J Med Microbiol 58, 217–221.[CrossRef]
    [Google Scholar]
  9. Ito, H., Arakawa, Y., Ohsuka, S., Wacharotayankun, R., Kato, N. & Ohta, M. ( 1995; ). Plasmid-mediated dissemination of the metallo-β-lactamase gene bla IMP among clinically isolated strains of Serratia marcescens. Antimicrob Agents Chemother 39, 824–829.[CrossRef]
    [Google Scholar]
  10. Iyobe, S., Kusadokoro, H., Takahashi, A., Yomoda, S., Okubo, T., Nakamura, A. & O'Hara, K. ( 2002; ). Detection of a variant metallo-β-lactamase, IMP-10, from two unrelated strains of Pseudomonas aeruginosa and an Alcaligenes xylosoxidans strain. Antimicrob Agents Chemother 46, 2014–2016.[CrossRef]
    [Google Scholar]
  11. Lahey Clinic ( 2008; ). Amino acid sequences for TEM, SHV and OXA extended-spectrum and inhibitor resistant β-lactamases. http://www.lahey.org/Studies (accessed 15 December 2008).
  12. Lévesque, C., Brassard, S., Lapointe, J. & Roy, P. H. ( 1994; ). Diversity and relative strength of tandem promoters for the antibiotic-resistance genes of several integrons. Gene 142, 49–54.[CrossRef]
    [Google Scholar]
  13. Li, X.-Z., Zhang, L. & Poole, K. ( 2000; ). Interplay between the MexA–MexB–OprM multidrug efflux system and the outer membrane barrier in the multiple antibiotic resistance of Pseudomonas aeruginosa. J Antimicrob Chemother 45, 433–436.[CrossRef]
    [Google Scholar]
  14. Livermore, D. M. & Woodford, N. ( 2000; ). Carbapenemases: a problem in waiting? Curr Opin Microbiol 3, 489–495.[CrossRef]
    [Google Scholar]
  15. Masuda, N., Gotoh, N., Ishii, C., Sakagawa, E., Ohya, S. & Nishino, T. ( 1999; ). Interplay between chromosomal β-lactamase and the MexAB–OprM efflux system in intrinsic resistance to β-lactams in Pseudomonas aeruginosa. Antimicrob Agents Chemother 43, 400–402.
    [Google Scholar]
  16. Mazel, D. ( 2006; ). Integrons: agents of bacterial evolution. Nat Rev Microbiol 4, 608–620.[CrossRef]
    [Google Scholar]
  17. NCCLS ( 2000; ). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, 5th edn, approved standard M7–A5. Wayne, PA: National Committee for Clinical Laboratory Standards.
  18. Nikaido, H. ( 1989; ). Outer membrane barrier as a mechanism of antimicrobial resistance. Antimicrob Agents Chemother 33, 1831–1836.[CrossRef]
    [Google Scholar]
  19. Nikaido, H. ( 1996; ). Multidrug efflux pumps of Gram-negative bacteria. J Bacteriol 178, 5853–5859.
    [Google Scholar]
  20. Osano, E., Arakawa, Y., Wacharotayankun, R., Ohta, M., Horii, T., Ito, H., Yoshimura, F. & Kato, N. ( 1994; ). Molecular characterization of an enterobacterial metallo β-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob Agents Chemother 38, 71–78.[CrossRef]
    [Google Scholar]
  21. Pai, H., Kim, J., Kim, J., Lee, J. H., Choe, K. W. & Gotoh, N. ( 2001; ). Carbapenem resistance mechanisms in Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother 45, 480–484.[CrossRef]
    [Google Scholar]
  22. Poirel, L., Naas, T., Nicolas, D., Collet, L., Bellais, S., Cavallo, J. D. & Nordmann, P. ( 2000; ). Characterization of VIM-2, a carbapenem-hydrolyzing metallo-β-lactamase and its plasmid- and integron-borne gene from a Pseudomonas aeruginosa clinical isolate in France. Antimicrob Agents Chemother 44, 891–897.[CrossRef]
    [Google Scholar]
  23. Quale, J., Bratu, S., Gupta, J. & Landman, D. ( 2006; ). Interplay of efflux system, ampC, and oprD expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother 50, 1633–1641.[CrossRef]
    [Google Scholar]
  24. Shibata, N., Doi, Y., Yamane, K., Yagi, T., Kurokawa, H., Shibayama, K., Kato, H., Kai, K. & Arakawa, Y. ( 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, 5407–5413.[CrossRef]
    [Google Scholar]
  25. Stokes, H. W. & Hall, R. M. ( 1989; ). A novel family of potentially mobile DNA elements encoding site-specific gene-integration functions: integrons. Mol Microbiol 3, 1669–1683.[CrossRef]
    [Google Scholar]
  26. Takeda, S., Nakai, T., Ikeda, F. & Hatano, K. ( 2008; ). Overproduction of a metallo-β-lactamase by a strong promoter causes high-level imipenem resistance in a clinical isolate of Pseudomonas aeruginosa. Chemotherapy 54, 181–187.[CrossRef]
    [Google Scholar]
  27. Tenover, F. C., Arbeit, R. D., Goering, R. V., Mickelsen, P. A., Murray, B. E., Persing, D. H. & Swaminathan, B. ( 1995; ). Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33, 2233–2239.
    [Google Scholar]
  28. Walsh, T. R., Toleman, M. A., Poirel, L. & Nordmann, P. ( 2005; ). Metallo-β-lactamases: the quiet before the storm? Clin Microbiol Rev 18, 306–325.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.010017-0
Loading
/content/journal/jmm/10.1099/jmm.0.010017-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error