임상 검체분리 Pseudomonas spp. 및 Acinetobacter spp.에서 검출된 blaVIM-2 카세트 보유 인테그론 구조의 다양성 = Diversity of Integrons Carrying blaVIM-2 Cassette in Pseudomonas spp. and Acinetobacter spp.

다국어 초록 (Multilingual Abstract)

Background: Metallo-β-lactamase-mediated carbapenem resistance has been increasingly reported in Pseudomonas, Acinetobacter and other Gram-negative bacilli (GNB) in many countries. A few studies showed highly variable structure of MBL-gene cassette-carrying integrons. The aim of this study was to determine the structure of blaVIM-2-carrying integrons in Pseudomonas and Acinetobacter.
Methods: blaVIM-2-carrying GNB were isolated at a Korean hospitals during the years 1995-1999 and 2005. The size of blaVIM-2-carrying integrons was estimated by the PCR products. Representative integrons were sequenced by the dideoxy-chain termination method. The MICs of antimicrobial agents were tested by the CLSI agar dilution methods.
Results: During the years 1995-1999 and 2005, the approximate size of the blaVIM-2-carrying class 1 integrons was 3-7 kb in 35 Pseudomonas isolates and 3-5 kb in 24 Acinetobacter isolates. The integrons carried one-five resistance gene cassettes in addition to the blaVIM-2 cassette. Other resistance gene cassettes found were blaOXA-1, aacA1, aac(6’)-I, and aac(6’)-II. Interestingly, sequences homologous to part of a putative class II intron were inserted into the recombination site of the last cassette in four of nine integrons. The class 1 integron from P. aeruginosa isolates had fused orf/IntI1 in a downstream leftward inverted repeat (IRi).
Conclusion: According to period, the size and structure of blaVIM-2-carrying integrons are quite variable,but an identical one is also present in a different genus,indicating high mobility of the blaVIM-2 cassette and horizontal transfer of the whole integron. We suggest that the class 1 integron containing the blaVIM-2gene is spreading horizontally among Gram- negative bacilli and is undergoing continuous development in Korea.

참고문헌 (Reference)

1 이경원, "지난 50년간 국내 항생제 내성의 변화와 향후 전망 - 그람음성 세균" 대한감염학회 43 (43): 458-467, 2011

2 Lee K, "blaVIM-2 cassette-containing novel integrons in metallo-betalactamase- producing Pseudomonas aeruginosa and Pseudomonas putida isolates disseminated in a Korean hospital" 46 : 1053-1058, 2002

3 Nobuta K, "Sequencing and expression of the 6'-N-acetyltransferase gene of transposon Tn1331 from Klebsiella pneumoniae" 170 : 3769-3773, 1988

4 Lee K, "Reduced imipenem susceptibility in Klebsiella pneumoniae clinical isolates with plasmid-mediated CMY-2 and DHA-1 beta-lactamases co-mediated by porin loss" 29 : 201-206, 2007

5 Clinical and Laboratory Standards Institute, "Performance standards for antimicrobial susceptibility testing; fifteenth informational supplement" Clinical and Laboratory Standards Institute 2005

6 Lee K, "Novel acquired metallo-beta-lactamase gene, blaSIM-1, in a class 1 integron from Acinetobacter baumannii clinical isolates from Korea" 49 : 4485-4491, 2005

7 Pallecchi L, "Molecular heterogeneity of blaVIM-2-containing integrons from Pseudomonas aeruginosa plasmids encoding the VIM-2 metallobeta- lactamase" 195 : 145-150, 2001

8 Yum JH, "Molecular characterization of metallo-beta-lactamase-producing Acinetobacter baumannii and Acinetobacter genomospecies 3 from Korea: identification of two new integrons carrying the blaVIM-2 gene cassettes" 49 : 837-840, 2002

9 Hall RM, "Mobile gene cassettes and integrons: capture and spread of genes by site-specific recombination" 15 : 593-600, 1995

10 Walsh TR, "Metallo-betalactamases: the quiet before the storm?" 18 : 306-325, 2005

11 Gupta V., "Metallo beta lactamases in Pseudomonas aeruginosa and Acinetobacter species" 17 : 131-143, 2008

12 Sekiguchi J, "KHM-1, a novel plasmid-mediated metallo-beta-lactamase from a Citrobacter freundii clinical isolate" 52 : 4194-4197, 2008

13 Riccio ML, "Fontana R, et al. Characterization of the metallo-beta-lactamase determinant of Acinetobacter baumannii AC-54/97 reveals the existence of blaIMP allelic variants carried by gene cassettes of different phylogeny" 44 : 1229-1235, 2000

14 Walsh TR, "Evolution of an integron carrying blaVIM-2 in Eastern Europe: report from the SENTRY Antimicrobial Surveillance Program" 52 : 116-119, 2003

15 Lee H, "Dissemination of 16S rRNA methylase-mediated highly amikacinresistant isolates of Klebsiella pneumoniae and Acinetobacter baumannii in Korea" 56 : 305-312, 2006

16 Levesque C, "Diagnostic Molecular Microbiology: Principles and Applications" American Society for Microbiology 590-594, 1993

17 Yong D, "Characterization of a new metallo-beta-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India" 53 : 5046-5054, 2009

18 이상희, "Characterization of a new integron containing VIM-2, a metallo-beta-lactamase gene cassette, in a clinical isolate of Enterobacter cloacae" OXFORD UNIV PRESS 51 : 397-400, 200302

19 Poirel L, "Characterization of VIM-2, a carbapenem-hydrolyzing metallo-betalactamase and its plasmid- and integron-borne gene from a Pseudomonas aeruginosa clinical isolate in France" 44 : 891-897, 2000

20 Poirel L, "Characterization of DIM-1, an integron-encoded metallo-beta-lactamase from a Pseudomonas stutzeri clinical isolate in the Netherlands" 54 : 2420-2424, 2010

21 Poirel L, "Characterization of Class 1 integrons from Pseudomonas aeruginosa that contain the blaVIM-2 carbapenem-hydrolyzing betalactamase gene and of two novel aminoglycoside resistance gene cassettes" 45 : 546-552, 2001

22 Papp-Wallace KM, "Carbapenems: past, present, and future" 55 : 4943-4960, 2011

23 Mingeot-Leclercq MP, "Aminoglycosides: activity and resistance" 43 : 727-737, 1999

24 Yum JH, "A new integron carrying VIM-2 metallo-beta-lactamase gene cassette in a Serratia marcescens isolate" 42 : 217-219, 2002