Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Apr;39(4):824–829. doi: 10.1128/aac.39.4.824

Plasmid-mediated dissemination of the metallo-beta-lactamase gene blaIMP among clinically isolated strains of Serratia marcescens.

H Ito 1, Y Arakawa 1, S Ohsuka 1, R Wacharotayankun 1, N Kato 1, M Ohta 1
PMCID: PMC162636  PMID: 7785978

Abstract

The distribution of strains producing metallo-beta-lactamase among 105 strains of Serratia marcescens was investigated. All of these strains were isolated in seven general hospitals located in Aichi Prefecture, Japan, from April to May 1993. Southern hybridization analysis suggested that four S. marcescens strains, AK9373, AK9374, AK9385, and AK9391, had a metallo-beta-lactamase genes similar to the blaIMP gene found by our laboratory (E. Osano, Y. Arakawa, R. Wacharotayankun, M. Ohta, T. Horii, H. Ito, F. Yoshimura, and N. Kato, Antimicrob. Agents Chemother. 38:71-78, 1994), and these four strains showed resistance to carbapenems as well as to the other broad-spectrum beta-lactams. In particular, strains AK9373, AK9374, and AK9391 showed an extraordinarily high-level resistance to imipenem (MICs, > or = 64 micrograms/ml), whereas strain AK9385 demonstrated moderate imipenem resistance (MIC, 8 micrograms/ml). The imipenem resistance of AK9373 was transferred to Escherichia coli CSH2 by conjugation with a frequency of 10(-5). The DNA probe of the blaIMP gene hybridized to a large plasmid (approximately 120 kb) transferred into the E. coli transconjugant as well as to the large plasmids harbored by AK9373. On the other hand, although we failed in the conjugational transfer of imipenem resistance from strains AK9374, AK9385, and AK9391 to E. coli CSH2, imipenem resistance was transferred from these strains to E. coli HB101 by transformation. A plasmid (approximately 25 kb) was observed in each transformant which acquired imipenem resistance. The amino acid sequence at the N terminus of the enzyme purified from strain AK9373 was identical to that of the metallo-beta-lactamase IMP-1. In contrast, strains ES9348, AK9386, and AK93101, which were moderately resistant to imipenem (MICs, > or = 4 to < or = 8 micrograms/ml), had no detectable blaIMP gene. As a conclusion, 19% of clinically isolated S. marcescens strains in Aichi Prefecture, Japan, in 1993 were resistant to imipenem (MICs, > or = 2 micrograms/ml), and strains which showed high-level imipenem resistance because of acquisition of a plasmid-mediated blaIMP-like metallo-beta-lactamase gene had already proliferated as nosocomial infections, at least in a general hospital.

Full Text

The Full Text of this article is available as a PDF (323.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arakawa Y., Ohta M., Kido N., Fujii Y., Komatsu T., Kato N. Close evolutionary relationship between the chromosomally encoded beta-lactamase gene of Klebsiella pneumoniae and the TEM beta-lactamase gene mediated by R plasmids. FEBS Lett. 1986 Oct 20;207(1):69–74. doi: 10.1016/0014-5793(86)80014-x. [DOI] [PubMed] [Google Scholar]
  2. Arakawa Y., Ohta M., Kido N., Mori M., Ito H., Komatsu T., Fujii Y., Kato N. Chromosomal beta-lactamase of Klebsiella oxytoca, a new class A enzyme that hydrolyzes broad-spectrum beta-lactam antibiotics. Antimicrob Agents Chemother. 1989 Jan;33(1):63–70. doi: 10.1128/aac.33.1.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bandoh K., Watanabe K., Muto Y., Tanaka Y., Kato N., Ueno K. Conjugal transfer of imipenem resistance in Bacteroides fragilis. J Antibiot (Tokyo) 1992 Apr;45(4):542–547. doi: 10.7164/antibiotics.45.542. [DOI] [PubMed] [Google Scholar]
  4. Bush K., Macalintal C., Rasmussen B. A., Lee V. J., Yang Y. Kinetic interactions of tazobactam with beta-lactamases from all major structural classes. Antimicrob Agents Chemother. 1993 Apr;37(4):851–858. doi: 10.1128/aac.37.4.851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cuchural G. J., Jr, Malamy M. H., Tally F. P. Beta-lactamase-mediated imipenem resistance in Bacteroides fragilis. Antimicrob Agents Chemother. 1986 Nov;30(5):645–648. doi: 10.1128/aac.30.5.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Horii T., Arakawa Y., Ohta M., Ichiyama S., Wacharotayankun R., Kato N. Plasmid-mediated AmpC-type beta-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum beta-lactams, including moxalactam. Antimicrob Agents Chemother. 1993 May;37(5):984–990. doi: 10.1128/aac.37.5.984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Horii T., Arakawa Y., Ohta M., Sugiyama T., Wacharotayankun R., Ito H., Kato N. Characterization of a plasmid-borne and constitutively expressed blaMOX-1 gene encoding AmpC-type beta-lactamase. Gene. 1994 Feb 11;139(1):93–98. doi: 10.1016/0378-1119(94)90529-0. [DOI] [PubMed] [Google Scholar]
  8. Inokuchi K., Itoh M., Mizushima S. Domains involved in osmoregulation of the ompF gene in Escherichia coli. J Bacteriol. 1985 Nov;164(2):585–590. doi: 10.1128/jb.164.2.585-590.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jacoby G. A., Medeiros A. A. More extended-spectrum beta-lactamases. Antimicrob Agents Chemother. 1991 Sep;35(9):1697–1704. doi: 10.1128/aac.35.9.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jarlier V., Nicolas M. H., Fournier G., Philippon A. Extended broad-spectrum beta-lactamases conferring transferable resistance to newer beta-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Rev Infect Dis. 1988 Jul-Aug;10(4):867–878. doi: 10.1093/clinids/10.4.867. [DOI] [PubMed] [Google Scholar]
  11. Kado C. I., Liu S. T. Rapid procedure for detection and isolation of large and small plasmids. J Bacteriol. 1981 Mar;145(3):1365–1373. doi: 10.1128/jb.145.3.1365-1373.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kitzis M. D., Billot-Klein D., Goldstein F. W., Williamson R., Tran Van Nhieu G., Carlet J., Acar J. F., Gutmann L. Dissemination of the novel plasmid-mediated beta-lactamase CTX-1, which confers resistance to broad-spectrum cephalosporins, and its inhibition by beta-lactamase inhibitors. Antimicrob Agents Chemother. 1988 Jan;32(1):9–14. doi: 10.1128/aac.32.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lindberg F., Normark S. Sequence of the Citrobacter freundii OS60 chromosomal ampC beta-lactamase gene. Eur J Biochem. 1986 May 2;156(3):441–445. doi: 10.1111/j.1432-1033.1986.tb09601.x. [DOI] [PubMed] [Google Scholar]
  14. Livermore D. M. Interplay of impermeability and chromosomal beta-lactamase activity in imipenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1992 Sep;36(9):2046–2048. doi: 10.1128/aac.36.9.2046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Malouin F., Campbell G. D., Halpenny M., Becker G. W., Parr T. R., Jr Outer membrane and porin characteristics of Serratia marcescens grown in vitro and in rat intraperitoneal diffusion chambers. Infect Immun. 1990 May;58(5):1247–1253. doi: 10.1128/iai.58.5.1247-1253.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Massidda O., Rossolini G. M., Satta G. The Aeromonas hydrophila cphA gene: molecular heterogeneity among class B metallo-beta-lactamases. J Bacteriol. 1991 Aug;173(15):4611–4617. doi: 10.1128/jb.173.15.4611-4617.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Matsumoto Y., Ikeda F., Kamimura T., Yokota Y., Mine Y. Novel plasmid-mediated beta-lactamase from Escherichia coli that inactivates oxyimino-cephalosporins. Antimicrob Agents Chemother. 1988 Aug;32(8):1243–1246. doi: 10.1128/aac.32.8.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Naas T., Vandel L., Sougakoff W., Livermore D. M., Nordmann P. Cloning and sequence analysis of the gene for a carbapenem-hydrolyzing class A beta-lactamase, Sme-1, from Serratia marcescens S6. Antimicrob Agents Chemother. 1994 Jun;38(6):1262–1270. doi: 10.1128/aac.38.6.1262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Neu H. C., Chin N. X., Saha G., Labthavikul P. In vitro activity against aerobic and anaerobic gram-positive and gram-negative bacteria and beta-lactamase stability of RS-533, a novel carbapenem. Antimicrob Agents Chemother. 1986 Dec;30(6):828–834. doi: 10.1128/aac.30.6.828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nomura K., Yoshida T. Nucleotide sequence of the Serratia marcescens SR50 chromosomal ampC beta-lactamase gene. FEMS Microbiol Lett. 1990 Aug;58(3):295–299. doi: 10.1111/j.1574-6968.1990.tb13992.x. [DOI] [PubMed] [Google Scholar]
  21. Nordmann P., Mariotte S., Naas T., Labia R., Nicolas M. H. Biochemical properties of a carbapenem-hydrolyzing beta-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli. Antimicrob Agents Chemother. 1993 May;37(5):939–946. doi: 10.1128/aac.37.5.939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Osano E., Arakawa Y., Wacharotayankun R., Ohta M., Horii T., Ito H., Yoshimura F., Kato N. Molecular characterization of an enterobacterial metallo beta-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob Agents Chemother. 1994 Jan;38(1):71–78. doi: 10.1128/aac.38.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Papanicolaou G. A., Medeiros A. A., Jacoby G. A. Novel plasmid-mediated beta-lactamase (MIR-1) conferring resistance to oxyimino- and alpha-methoxy beta-lactams in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother. 1990 Nov;34(11):2200–2209. doi: 10.1128/aac.34.11.2200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Quinn J. P., Dudek E. J., DiVincenzo C. A., Lucks D. A., Lerner S. A. Emergence of resistance to imipenem during therapy for Pseudomonas aeruginosa infections. J Infect Dis. 1986 Aug;154(2):289–294. doi: 10.1093/infdis/154.2.289. [DOI] [PubMed] [Google Scholar]
  25. Rasmussen B. A., Gluzman Y., Tally F. P. Cloning and sequencing of the class B beta-lactamase gene (ccrA) from Bacteroides fragilis TAL3636. Antimicrob Agents Chemother. 1990 Aug;34(8):1590–1592. doi: 10.1128/aac.34.8.1590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rasmussen B. A., Yang Y., Jacobus N., Bush K. Contribution of enzymatic properties, cell permeability, and enzyme expression to microbiological activities of beta-lactams in three Bacteroides fragilis isolates that harbor a metallo-beta-lactamase gene. Antimicrob Agents Chemother. 1994 Sep;38(9):2116–2120. doi: 10.1128/aac.38.9.2116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanders C. C. Chromosomal cephalosporinases responsible for multiple resistance to newer beta-lactam antibiotics. Annu Rev Microbiol. 1987;41:573–593. doi: 10.1146/annurev.mi.41.100187.003041. [DOI] [PubMed] [Google Scholar]
  28. Seeberg A. H., Tolxdorff-Neutzling R. M., Wiedemann B. Chromosomal beta-lactamases of Enterobacter cloacae are responsible for resistance to third-generation cephalosporins. Antimicrob Agents Chemother. 1983 Jun;23(6):918–925. doi: 10.1128/aac.23.6.918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  30. Tada Y., Yamaguchi J. A function of 40 kDa outer membrane protein in Serratia marcescens. Microbiol Immunol. 1994;38(3):171–175. doi: 10.1111/j.1348-0421.1994.tb01761.x. [DOI] [PubMed] [Google Scholar]
  31. Takeshita S., Sato M., Toba M., Masahashi W., Hashimoto-Gotoh T. High-copy-number and low-copy-number plasmid vectors for lacZ alpha-complementation and chloramphenicol- or kanamycin-resistance selection. Gene. 1987;61(1):63–74. doi: 10.1016/0378-1119(87)90365-9. [DOI] [PubMed] [Google Scholar]
  32. Vartivarian S., Anaissie E., Bodey G., Sprigg H., Rolston K. A changing pattern of susceptibility of Xanthomonas maltophilia to antimicrobial agents: implications for therapy. Antimicrob Agents Chemother. 1994 Mar;38(3):624–627. doi: 10.1128/aac.38.3.624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Watanabe M., Iyobe S., Inoue M., Mitsuhashi S. Transferable imipenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1991 Jan;35(1):147–151. doi: 10.1128/aac.35.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yang Y. J., Wu P. J., Livermore D. M. Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates. Antimicrob Agents Chemother. 1990 May;34(5):755–758. doi: 10.1128/aac.34.5.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES