Dongeun Yong

doi:10.5145/KJCM.2009.12.3.103

Journal List > Korean J Clin Microbiol > v.12(3) > 1038160

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Yong: Metallo-β-lactamase Producing Gram-negative Bacilli

Original Article

Korean J Clin Microbiol 2009;12(3):103-109.

Published online: 22 September 2009

DOI: https://doi.org/10.5145/KJCM.2009.12.3.103

Metallo-β-lactamase Producing Gram-negative Bacilli

Dongeun Yong

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, Korea

Correspondence: Dongeun Yong, Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, 250, Seongsan-ro, Seodaemun-gu, Seoul 120-752, Korea. (Tel) 82-2-2228-2446, (Fax) 82-2-313-0956, (E-mail) deyong@yuhs.ac

Received 8 June 200919 August 2009 Accepted 25 August 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Among gram-negative bacteria, rate of antibiotic resistance has been increasing. As a result, carbapenem is now considered as a last resort of therapeutic regimens for gram-negative bacterial infections. The choice of antibiotics has been impeded by the spread of organisms producing metallo-β-lactamases (MBL), which can confer resistance to nearly all β-lactams. MBLs have extremely diverse structures and are carried by various organisms including human pathogens. This review will focus on the classification and current status of MBL reported in Korea.

Keywords: Metallo- β-lactamase, Gram-negative bacilli

REFERENCES

1. Rossolini GM, Docquier JD. Class B β-lactamases. Bonomo RA, Tomasky ME, editors. eds.Enzyme-mediated Resistance to Antibiotics: Mechanisms, Dissemination, and Prospects for Inhibition. Washington, DC.: ASM Press;2007. p. 115–44.

2. Kim YS. Biochemistry. 1st ed.Seoul: Shinkwang;1987. 7:p. 1–8.

3. Nordmann P, Mariotte S, Naas T, Labia R, Nicolas MH. Biochemical properties of a carbapenem-hydrolyzing beta-lactamase from Enterobacter cloacae and cloning of the gene into Escherichia coli. Antimicrob Agents Chemother. 1993; 37:939–46.

4. Poirel L, Weldhagen GF, Naas T, De Champs C, Dove MG, Nordmann P. GES-2, a class A beta-lactamase from Pseudomonas aeruginosa with increased hydrolysis of imipenem. Antimicrob Agents Chemother. 2001; 45:2598–603.

5. Queenan AM, Torres-Viera C, Gold HS, Carmeli Y, Eliopoulos GM, Moellering RC Jr, et al. SME-type carbapenem-hydrolyzing class A beta-lactamases from geographically diverse Serratia marcescens strains. Antimicrob Agents Chemother. 2000; 44:3035–9.

6. Rasmussen BA, Bush K, Keeney D, Yang Y, Hare R, O'Gara C, et al. Characterization of IMI-1 beta-lactamase, a class A carbapenem-hydrolyzing enzyme from Enterobacter cloacae. Antimicrob Agents Chemother. 1996; 40:2080–6.

7. Yang YJ, Wu PJ, Livermore DM. Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates. Antimicrob Agents Chemother. 1990; 34:755–8.

8. Yigit H, Queenan AM, Anderson GJ, Domenech-Sanchez A, Biddle JW, Steward CD, et al. Novel carbapenem-hydrolyzing beta-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother. 2001; 45:1151–61.

9. Nordmann P, Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect. 2002; 8:321–31.

10. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007; 20:440–58.

11. Rasmussen BA, Bush K. Carbapenem-hydrolyzing beta-lactamases. Antimicrob Agents Chemother. 1997; 41:223–32.

12. Walsh TR, Toleman MA, Poirel L, Nordmann P. Metallo-beta-lactamases: the quiet before the storm? Clin Microbiol Rev. 2005; 18:306–25.

13. Sekiguchi J, Morita K, Kitao T, Watanabe N, Okazaki M, Miyoshi-Akiyama T, et al. KHM-1, a novel plasmid-mediated metallo-beta-lactamase from a Citrobacter freundii clinical isolate. Antimicrob Agents Chemother. 2008; 52:4194–7.

14. Watanabe M, Iyobe S, Inoue M, Mitsuhashi S. Transferable imipenem resistance in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1991; 35:147–51.

15. Castanheira M, Toleman MA, Jones RN, Schmidt FJ, Walsh TR. Molecular characterization of a beta-lactamase gene, blaGIM-1, encoding a new subclass of metallo-beta-lactamase. Antimicrob Agents Chemother. 2004; 48:4654–61.

16. Lauretti L, Riccio ML, Mazzariol A, Cornaglia G, Amicosante G, Fontana R, et al. Cloning and characterization of blaVIM, a new integron-borne metallo-beta-lactamase gene from a Pseudomonas aeruginosa clinical isolate. Antimicrob Agents Chemother. 1999; 43:1584–90.

17. Poirel L, Lambert T, Türkoglü S, Ronco E, Gaillard J, Nordmann P. Characterization of Class 1 integrons from Pseudomonas aeruginosa that contain the bla(VIM-2) carbapenem-hydrolyzing beta-lactamase gene and of two novel aminoglycoside resistance gene cassettes. Antimicrob Agents Chemother. 2001; 45:546–52.

18. Toleman MA, Biedenbach D, Bennett D, Jones RN, Walsh TR. Genetic characterization of a novel metallo-beta-lactamase gene, blaIMP-13, harboured by a novel Tn5051-type transposon disseminating carbapenemase genes in Europe: report from the SENTRY worldwide antimicrobial surveillance programme. J Antimicrob Chemother. 2003; 52:583–90.

19. Toleman MA, Bennett PM, Walsh TR. ISCR elements: novel gene-capturing systems of the 21st century? Microbiol Mol Biol Rev. 2006; 70:296–316.

20. Toleman MA, Rolston K, Jones RN, Walsh TR. blaVIM-7, an evolutionarily distinct metallo-beta-lactamase gene in a Pseudomonas aeruginosa isolate from the United States. Antimicrob Agents Chemother. 2004; 48:329–32.

21. Osano E, Arakawa Y, Wacharotayankun R, Ohta M, Horii T, Ito H, et al. Molecular characterization of an enterobacterial metallo beta-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob Agents Chemother. 1994; 38:71–8.

22. Arakawa Y, Shibata N, Shibayama K, Kurokawa H, Yagi T, Fujiwara H, et al. Convenient test for screening metallo-beta-lactamase-producing gram-negative bacteria by using thiol compounds. J Clin Microbiol. 2000; 38:40–3.

23. Riccio ML, Franceschini N, Boschi L, Caravelli B, Cornaglia G, Fontana R, et al. Characterization of the metallo-beta-lactamase determinant of Acinetobacter baumannii AC-54/97 reveals the existence of bla(IMP) allelic variants carried by gene cassettes of different phylogeny. Antimicrob Agents Chemother. 2000; 44:1229–35.

24. Daiyasu H, Osaka K, Ishino Y, Toh H. Expansion of the zinc metallo-hydrolase family of the beta-lactamase fold. FEBS Lett. 2001; 503:1–6.

25. Chu YW, Afzal-Shah M, Houang ET, Palepou MI, Lyon DJ, Woodford N, et al. IMP-4, a novel metallo-beta-lactamase from nosocomial Acinetobacter spp. collected in Hong Kong between 1994 and 1998. Antimicrob Agents Chemother. 2001; 45:710–4.

26. Lee K, Lee WG, Uh Y, Ha GY, Cho J, Chong Y. VIM- and IMP-type metallo-beta-lactamase-producing Pseudomonas spp. and Acinetobacter spp. in Korean hospitals. Emerg Infect Dis. 2003; 9:868–71.

27. Lee K, Chong Y, Yong D, Yum JH, Chong S. Evolution of Resistance and Spread of Multidrug-resistant Bacteria. Seoul: Seoheung Press Inc.;2007. p. 128–51.

28. Lombardi G, Luzzaro F, Docquier JD, Riccio ML, Perilli M, Colí A, et al. Nosocomial infections caused by multidrug-resistant isolates of Pseudomonas putida producing VIM-1 metallo-beta-lactamase. J Clin Microbiol. 2002; 40:4051–5.

29. Riccio ML, Pallecchi L, Fontana R, Rossolini GM. In70 of plasmid pAX22, a bla(VIM-1)-containing integron carrying a new aminoglycoside phosphotransferase gene cassette. Antimicrob Agents Chemother. 2001; 45:1249–53.

30. Poirel L, Collet L, Nordmann P. Carbapenem-hydrolyzing metallo-beta-lactamase from a nosocomial isolate of Pseudomonas aeruginosa in France. Emerg Infect Dis. 2000; 6:84–5.

31. Lee K, Lim JB, Yum JH, Yong D, Chong Y, Kim JM, et al. bla (VIM-2) cassette-containing novel integrons in metallo-beta-lactamase-producing Pseudomonas aeruginosa and Pseudomonas putida isolates disseminated in a Korean hospital. Antimicrob Agents Chemother. 2002; 46:1053–8.

32. Toleman MA, Simm AM, Murphy TA, Gales AC, Biedenbach DJ, Jones RN, et al. Molecular characterization of SPM-1, a novel metallo-beta-lactamase isolated in Latin America: report from the SENTRY antimicrobial surveillance programme. J Antimicrob Chemother. 2002; 50:673–9.

33. Yum JH, Yi K, Lee H, Yong D, Lee K, Kim JM, et al. Molecular characterization of metallo-beta-lactamase-producing Acinetobacter baumannii and Acinetobacter genomospecies 3 from Korea: identification of two new integrons carrying the bla(VIM-2) gene cassettes. J Antimicrob Chemother. 2002; 49:837–40.

34. Oh EJ, Lee S, Park YJ, Park JJ, Park K, Kim SI, et al. Prevalence of metallo-beta-lactamase among Pseudomonas aeruginosa and Acinetobacter baumannii in a Korean university hospital and comparison of screening methods for detecting metallo-beta-lactamase. J Microbiol Methods. 2003; 54:411–8.

35. Lee K, Ha GY, Shin BM, Kim JJ, Kang JO, Jang SJ, et al. Metallo-beta-lactamase-producing Gram-negative bacilli in Korean Nationwide Surveillance of Antimicrobial Resistance group hospitals in 2003: continued prevalence of VIM-producing Pseudomonas spp. and increase of IMP-producing Acinetobacter spp. Diagn Microbiol Infect Dis. 2004; 50:51–8.

36. Ryoo NH, Lee K, Lim JB, Lee YH, Bae IK, Jeong SH. Outbreak by meropenem-resistant Pseudomonas aeruginosa producing IMP-6 metallo-beta-lactamase in a Korean hospital. Diagn Microbiol Infect Dis. 2009; 63:115–7.

37. Yum JH, Yong D, Lee K, Kim HS, Chong Y. A new integron carrying VIM-2 metallo-beta-lactamase gene cassette in a Serratia marcescens isolate. Diagn Microbiol Infect Dis. 2002; 42:217–9.

38. Yong D, Choi YS, Roh KH, Kim CK, Park YH, Yum JH, et al. Increasing prevalence and diversity of metallo-beta-lactamases in Pseudomonas spp., Acinetobacter spp., and Enterobacteriaceae from Korea. Antimicrob Agents Chemother. 2006; 50:1884–6.

39. Shin KS, Han K, Lee J, Hong SB, Son BR, Youn SJ, et al. Imipenem-resistant Achromobacter xylosoxidans carrying blaVIM-2-containing class 1 integron. Diagn Microbiol Infect Dis. 2005; 53.

40. Walsh TR, MacGowan AP, Bennett PM. Sequence analysis and enzyme kinetics of the L2 serine beta-lactamase from Stenotrophomonas maltophilia. Antimicrob Agents Chemother. 1997; 41:1460–4.

41. Podglajen I, Breuil J, Collatz E. Insertion of a novel DNA sequence, 1S1186, upstream of the silent carbapenemase gene cfiA, promotes expression of carbapenem resistance in clinical isolates of Bacteroides fragilis. Mol Microbiol. 1994; 12:105–14.

42. Yamazoe K, Kato N, Kato H, Tanaka K, Katagiri Y, Watanabe K. Distribution of the cfiA gene among Bacteroides fragilis strains in Japan and relatedness of cfiA to imipenem resistance. Antimicrob Agents Chemother. 1999; 43:2808–10.

43. Podglajen I, Breuil J, Casin I, Collatz E. Genotypic identification of two groups within the species Bacteroides fragilis by ribotyping and by analysis of PCR-generated fragment patterns and insertion sequence content. J Bacteriol. 1995; 177:5270–5.

44. Rossolini GM, Zanchi A, Chiesurin A, Amicosante G, Satta G, Guglielmetti P. Distribution of cphA or related carbapenemase-encoding genes and production of carbapenemase activity in members of the genus Aeromonas. Antimicrob Agents Chemother. 1995; 39:346–9.

45. Rossolini GM, Walsh T, Amicosante G. The Aeromonas metallo-beta-lactamases: genetics, enzymology, and contribution to drug resistance. Microb Drug Resist. 1996; 2:245–52.

46. Rossolini GM, Franceschini N, Riccio ML, Mercuri PS, Perilli M, Galleni M, et al. Characterization and sequence of the Chryseobacterium (Flavobacterium) meningosepticum carbapenemase: a new molecular class B beta-lactamase showing a broad substrate profile. Biochem J. 1998; 332:145–52.

47. Bellais S, Poirel L, Leotard S, Naas T, Nordmann P. Genetic diversity of carbapenem-hydrolyzing metallo-beta-lactamases from Chryseobacterium (Flavobacterium) indologenes. Antimicrob Agents Chemother. 2000; 44:3028–34.

48. Bellais S, Leotard S, Poirel L, Naas T, Nordmann P. Molecular characterization of a carbapenem-hydrolyzing beta-lactamase from Chryseobacterium (Flavobacterium) indologenes. FEMS Microbiol Lett. 1999; 171:127–32.

49. Institute CaLS. Performance standars for antimicrobial susceptibility testing; nineteenth information supplement. Vol M100-S19. Wayne, PA; Clinical and Laboratory Standards Institute,. 2009.

50. Yong D, Lee K, Yum JH, Shin HB, Rossolini GM, Chong Y. Imipenem-EDTA disk method for differentiation of metallo-beta-lactamase-producing clinical isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol. 2002; 40:3798–801.

51. Lee K, Lim YS, Yong D, Yum JH, Chong Y. Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-beta-lactamase-producing isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol. 2003; 41:4623–9.

52. Walsh TR, Bolmström A, Qwärnström A, Gales A. Evaluation of a new Etest for detecting metallo-beta-lactamases in routine clinical testing. J Clin Microbiol. 2002; 40:2755–9.

53. Shibata N, Doi Y, Yamane K, Yagi T, Kurokawa H, Shibayama K, et al. PCR typing of genetic determinants for metallo-beta-lactamases and integrases carried by gram-negative bacteria isolated in Japan, with focus on the class 3 integron. J Clin Microbiol. 2003; 41:5407–13.

54. Bellais S, Mimoz O, Leotard S, Jacolot A, Petitjean O, Nordmann P. Efficacy of beta-lactams for treating experimentally induced pneumonia due to a carbapenem-hydrolyzing metallo-beta-lactamase-producing strain of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2002; 46:2032–4.

55. Daikos GL, Panagiotakopoulou A, Tzelepi E, Loli A, Tzouvelekis LS, Miriagou V. Activity of imipenem against VIM-1 metallo-beta-lactamase-producing Klebsiella pneumoniae in the murine thigh infection model. Clin Microbiol Infect. 2007; 13:202–5.

56. Parkins MD, Pitout JD, Church DL, Conly JM, Laupland KB. Treatment of infections caused by metallo-beta-lactamase-producing Pseudomonas aeruginosa in the Calgary Health Region. Clin Microbiol Infect. 2007; 13:199–202.

57. Markou N, Apostolakos H, Koumoudiou C, Athanasiou M, Koutsoukou A, Alamanos I, et al. Intravenous colistin in the treatment of sepsis from multiresistant Gram-negative bacilli in critically ill patients. Crit Care. 2003; 7:R78–83.

Table 1.

Classification of MBLs[1,12,13]

Subgroup	Organism	Enzyme
B1 (chromosomal)	Bacillus cereus	BCII-5/B/6, BCII-569/H
	Bacillus anthracis	Bla2
	Chryseobacterium meningosepticum	BlaB, BlaB2-8
	Chryseobacterium gleum	CGB-1
	Myroides odoratus	TUS-1
	Myroides odoratimimus	MUS-1
	Flavobacterium johnsoniae	JOHN-1
	Bacteroides fragilis	CfiA/CcrA
B1 (transferable)	Pseudomonas spp.	IMP, VIM, SPM-1, GIM-1
	Acinetobacter spp.	IMP, VIM, SIM-1
	Escherichia coli	VIM, NDM-1
	Klebsiella pneumoniae	IMP, VIM, NDM-1
	Citrobacter freundii	IMP, VIM, KHM-1
	Enterobacter aerogenes	VIM
	Enterobacter cloacae	IMP, VIM
	Serratia marcescens	IMP, VIM
	Proteus mirabilis	VIM
	Providencia stuartii	VIM
	Shigella flexneri	IMP
	Achromobacter xylosoxidans	IMP, VIM
	Alcaligenes spp.	IMP
B2 (chromosomal)	Aeromonas hydrophilia	CphA
	Aeromonas veronii	ImiS, AsbM1
	Serratia fonticola	SFH-1
B3 (chromosomal)	Caulobacter crescentus	Mb11B, CAU-1
	Janthinobacterium lividium	THIN-B
	Legionella gormanii	FEZ-1
	Chryseobacterium meningosepticum	GOB-1-7
	Stenotrophomonas maltophilia	L1a, L1-BlaS, L1c, L1d, L1e
B3 (transferable)	Pseudomonas aeruginosa	AIM-1

Table 2.

IMP-type MBL[12,27]

MBL	Species	Nation
IMP-1	P. aeruginosa	Japan, Korea, Brazil
	P. putida, P. fluorescens	Japan, Singapore
	P. stutzeri	Japan
	Acinetobacter spp.	Japan, Korea, UK
IMP-2	Acinetobacter spp.	Japan, Italy
IMP-2	P. aeruginosa	Japan
IMP-3	Shigella flexneri	Japan
IMP-4	A. baumannii	Hong Kong
	C. freundii	China, Australia
	P. aeruginosa	China, Australia
IMP-5	A. baumannii	Portugal
IMP-5	P. aeruginosa	Korea
IMP-6	A. baumannii	Brazil
	S. marcescens	Japan
	P. aeruginosa	Korea
IMP-7	P. aeruginosa	Malaysia, Canada
IMP-8	E. cloacae, K. pneumoniae	Taiwan
IMP-9	P. aeruginosa	China
IMP-10	P. aeruginosa, A. xylosoxidans	Japan
IMP-11	P. aeruginosa, A. baumannii	Japan
IMP-12	P. putida	Italy
IMP-13	P. aeruginosa	Italy
IMP-14, 15	P. aeruginosa	Thailand
IMP-16	P. aeruginosa	Brazil
IMP-17,	Assigned	Assigned
-23, -24
IMP-18	P. aeruginosa	USA
IMP-19	Aeromonas punctata	France
IMP-20, -21	P. aeruginosa	Japan
IMP-22	P. fluorescens	Italy
IMP-25	P. aeruginosa	China
IMP-26	P. aeruginosa	Korea

Table 3.

VIM-type MBL[12,27]

MBL	Species	Nation
VIM-1	P. aeruginosa,	Italy
	P. putida
	A. xylosoxidans	Italy
	E. coli	Greece, France
	K. pneumoniae	Italy
VIM-2	A. baumannii,	Korea
	Acinetobacter spp.
	A. xylosoxidans	Japan
	P. aeruginosa	Korea, Japan, Italy, Greece,
		France, Spain, Portugal,
		Poland, Croatia, USA,
		Argentina, Chile, Venezuela
	P. putida	Korea, Japan
	P. fluorescens	Chile
	P. stutzeri	Taiwan
	C. freundii	Taiwan
	E. cloacae,	Korea
	S. marcescens
VIM-3	P. aeruginosa	Taiwan
VIM-4	P. aeruginosa	Greece, Poland, Sweden
	E. cloacae,	Italy
	K. pneumoniae
VIM-5	P. aeruginosa,	Turkey
VIM-5	K. pneumoniae
VIM-6	P. putida	Singapore
VIM-7	P. aeruginosa	USA
VIM-8	P. aeruginosa	Chile
VIM-9, 10	P. aeruginosa	UK
VIM-11	P. aeruginosa	Italy, Argentina
VIM-12	K. pneumoniae	Greece
VIM-13	P. aeruginosa	Spain, Korea
VIM-14	P. aeruginosa	Italy, Spain
VIM-15, -16	P. aeruginosa	Germany
VIM-17	P. aeruginosa	Greece
VIM-18	P. aeruginosa	India
VIM-19, 20, 21, 22	Assigned	Assigned

Table 4.

Methods for MBL detection[12,27]

Methods		Materials	Advantages	Disadvantage
Phenotype	Double disk synergy	CAZ or IPM plus	Easy	Need standardization, vague to read
		MPA or SMA
		IPM + EDTA/SMA	Easy	Need standardization, vague to read
	Disk potentiation	IMP vs. IMP+EDTA	Easy	Need standardization, false negative by EDTA
	Microdilution	IPM, EDTA, 1,10-phenanthroline	Easy	Labor intensive, false negative to IPM susceptible MBL producer
	E test	IPM, EDTA	Easy	False negative to IPM susceptible MBL
	Carbapenem hydrolysis	Spectrophotometer	Applicable to all MBL detection	Labor intensive, vague to read
			Standard methods
Genotype	PCR	Primer, thermocycler	Easy,	Primer design
			MBL type specific	May not applicable to New MBL type
	DNA probe	Probe, hybridizer		Group specific probe
	Cloning, sequencing	Nucleotide sequencer	Applicable to new MBL type	Labor intensive

TOOLS

Similar articles