期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 54, 期 2, 页码 825-834出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00959-09
关键词
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资金
- CIBERESP (Network Center for Biomedical Research in Epidemiology and Public Health) of Instituto Carlos III, Ministerio de Ciencia e Innovacion of Spain [CB06/02/0053]
- Fundacao para a Ciencia e Tecnologia de Portugal [SFRH/BD/11304/2002]
- European Commission [LSHM-CT-2008-223031, KBBE-2008-2B-227258, LSHM-CT-2005-018705]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/11304/2002] Funding Source: FCT
TEM-24 remains one of the most widespread TEM-type extended-spectrum beta-lactamases (ESBLs) among Enterobacteriaceae. To analyze the reasons influencing its spread and persistence, a multilevel population genetics study was carried out on 28 representative TEM-24 producers from Belgium, France, Portugal, and Spain (13 Enterobacter aerogenes isolates, 6 Escherichia coli isolates, 6 Klebsiella pneumoniae isolates, 2 Proteus mirabilis isolates, and 1 Klebsiella oxytoca isolate, from 1998 to 2004). Clonal relatedness (XbaI pulsed-field gel electrophoresis [PFGE] and E. coli phylogroups) and antibiotic susceptibility were determined by standard procedures. Plasmid analysis included determination of the incompatibility group (by PCR, hybridization, and/or sequencing) and comparison of restriction fragment length polymorphism (RFLP) patterns. Characterization of genetic elements conferring antibiotic resistance included integrons (classes 1, 2, and 3) and transposons (Tn3, Tn21, and Tn402). Similar PFGE patterns were identified among E. aerogenes, K. pneumoniae, and P. mirabilis isolates, while E. coli strains were diverse (phylogenetic groups A, B2, and D). Highly related 180-kb IncA/C-2 plasmids conferring resistance to kanamycin, tobramycin, chloramphenicol, trimethoprim, and sulfonamides were identified. Each plasmid contained defective In0-Tn402 (dfrA1-aadA1, aacA4, or aacA4-aacC1-orfE-aadA2-cmlA1) and In4-Tn402 (aacA4 or dfrA1-aadA1) variants. These integrons were located within Tn21, Tn1696, or hybrids of these transposons, with IS5075 interrupting their IRtnp and IRmer. In all cases, bla(TEM-24) was part of an IS5075-Delta Tn1 transposon within tnp(1696), mimicking other genetic elements containing bla(TEM-2) and bla(TEM-3) variants. The international dissemination of TEM-24 is fuelled by an IncA/C-2 plasmid acquired by different enterobacterial clones which seem to evolve by gaining diverse genetic elements. This work highlights the risks of a confluence between highly penetrating clones and highly promiscuous plasmids in the spread of antibiotic resistance, and it contributes to the elucidation of the origin and evolution of TEM-2 ESBL derivatives.
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