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Published on: March 16, 2012
blaCTX-M-1/9/1 Hybrid Genes May Have Been Generated from blaCTX-M-15 on an IncI2 Plasmid
Lanping Liu1, Dandan He1, Luchao Lv1
1College of Veterinary Medicine, Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, South China Agricultural University, Guangzhou, People's Republic of China.
Abstract:
Three hybrid CTX-M β-lactamases, CTX-M-64, CTX-M-123, and CTX-M-132, with N and C termini matching CTX-M-1 group enzymes and centers matching CTX-M-9 group enzymes, have been identified. The hybrid gene sequences suggested recombination between blaCTX-M-15 and blaCTX-M-14, the two most common blaCTX-M variants worldwide. However, blaCTX-M-64 and blaCTX-M-123 are found in an ISEcp1-blaCTX-M transposition unit with a 45-bp "spacer," rather than the 48 bp usually associated with blaCTX-M-15, and 112 bp of IncA/C plasmid backbone. This is closer to the context of blaCTX-M-55, which has one nucleotide difference from blaCTX-M-15, on IncI2 plasmid pHN1122-1. Here, we characterized an IncI2 plasmid carrying blaCTX-M-15 with a 45-bp spacer (pHNY2-1) by complete sequencing and also sequenced IncI2 plasmids carrying blaCTX-M-64 (pHNAH46-1) or blaCTX-M-132 (pHNLDH19) and an IncI1 plasmid carrying blaCTX-M-123 (pHNAH4-1). pHNY2-1 has the same ISEcp1-blaCTX-M-IncA/C insertion as pHN1122-1, pHNAH46-1, and pHNLDH19, and all four plasmid backbones are almost identical. pHNAH4-1 (IncI1 sequence type 108 [ST108]) carries a transposition unit that includes a 2,720-bp fragment of the IncI2 backbone, suggesting ISEcp1-mediated transfer of blaCTX-M-IncA/C-IncI2 to an IncI1 plasmid. All three hybrid blaCTX-M genes may have resulted from recombination between blaCTX-M-14 and blaCTX-M-15 with a 45-bp spacer on an IncI2 plasmid. Five additional Escherichia coli isolates of different sequence types from different provinces, farms, and/or animals had blaCTX-M-64 on a pHNAH46-1-like IncI2 plasmid and 9 had blaCTX-M-123 on a pHNAH4-1-like IncI1 ST108 plasmid. Thus, epidemic IncI plasmids may be responsible for the spread of blaCTX-M-64 and blaCTX-M-123 between different animals and different locations in China.
Insights
New hybrid CTX-M enzymes (CTX-M-64, CTX-M-123, CTX-M-132) likely arose from recombination between common blaCTX-M genes. Epidemic IncI plasmids are implicated in the spread of these novel beta-lactamases in China.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- CTX-M β-lactamases are a major cause of antimicrobial resistance.
- Hybrid CTX-M variants, such as CTX-M-64, CTX-M-123, and CTX-M-132, exhibit mosaic structures.
- These hybrids possess N and C termini similar to CTX-M-1 group enzymes and central regions resembling CTX-M-9 group enzymes.
Purpose of the Study:
- To characterize the genetic context and plasmid backbone of novel hybrid CTX-M β-lactamase genes.
- To investigate the potential origins and mechanisms of dissemination of these hybrid genes.
- To identify the role of IncI plasmids in the spread of CTX-M resistance.
Main Methods:
- Complete sequencing of IncI2 plasmids carrying blaCTX-M-15, blaCTX-M-64, and blaCTX-M-132.
- Sequencing of an IncI1 plasmid carrying blaCTX-M-123.
- Comparative analysis of plasmid backbones and transposition units.
Main Results:
- Hybrid blaCTX-M genes (CTX-M-64, CTX-M-123, CTX-M-132) were identified, likely resulting from recombination between blaCTX-M-14 and blaCTX-M-15.
- These genes were found within ISEcp1-blaCTX-M transposition units with a 45-bp spacer, often on IncI2 plasmids.
- Epidemic IncI plasmids (IncI1 and IncI2) carrying these hybrid genes were detected in multiple Escherichia coli isolates across China, suggesting widespread dissemination.
Conclusions:
- The identified hybrid CTX-M β-lactamases represent novel variants with potential clinical significance.
- Recombination events involving common blaCTX-M genes and specific plasmid contexts likely generated these hybrids.
- Epidemic IncI plasmids play a crucial role in the inter-animal and inter-regional spread of CTX-M resistance genes in China.
