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Plasmid-mediated extended-spectrum beta-lactamase (CTX-M-3 like) from India and gene association with insertion
A Karim1, L Poirel, S Nagarajan
1Service de Bacteriologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médicine Paris-Sud, France.
Abstract:
Six non-clonally related enterobacterial isolates producing a same extended-spectrum beta-lactamase CTX-M-15 were isolated in 1999 from patients hospitalized in a New Delhi hospital. CTX-M-15 differed from CTX-M-3 by an asparagine to glycine substitution in position ABL238. Its gene was located on large plasmids varying in size. In each case, a same insertion sequence ISEcp1 was identified upstream of the 5' end of bla(CTX-M-15). Typical -35 and -10 promoter sequences of Enterobacteriaceae were identified in the 3' end of ISEcp1. The location of ISEcp1 upstream of plasmid-mediated CTX-M-type beta-lactamase genes may contribute to their spread or/and their expression.
Insights
Extended-spectrum beta-lactamase CTX-M-15, identified in New Delhi, differs from CTX-M-3 by a key amino acid substitution. Its spread may be facilitated by the insertion sequence ISEcp1 on plasmids.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- Extended-spectrum beta-lactamases (ESBLs) are a growing public health concern, conferring resistance to crucial antibiotics.
- CTX-M-type ESBLs are increasingly prevalent globally, often associated with plasmid-mediated dissemination.
- The emergence of novel ESBL variants necessitates understanding their genetic basis and spread mechanisms.
Purpose of the Study:
- To characterize a novel extended-spectrum beta-lactamase, CTX-M-15, identified in enterobacterial isolates.
- To investigate the genetic environment and potential mechanisms of dissemination for the bla(CTX-M-15) gene.
Main Methods:
- Bacterial isolate characterization and antimicrobial susceptibility testing.
- Plasmid DNA analysis and sequencing to identify gene location and surrounding elements.
- Sequence analysis to compare CTX-M-15 with related beta-lactamases and identify genetic features like insertion sequences.
Main Results:
- Six non-clonally related enterobacterial isolates producing CTX-M-15 were identified in New Delhi.
- CTX-M-15 exhibited a single amino acid substitution (Asn to Gly at ABL238) compared to CTX-M-3.
- The bla(CTX-M-15) gene was located on large, variable-sized plasmids.
- The insertion sequence ISEcp1 was consistently found upstream of the bla(CTX-M-15) gene, containing promoter-like sequences.
Conclusions:
- The novel CTX-M-15 ESBL emerged in New Delhi, associated with a specific amino acid change.
- The presence of ISEcp1 upstream of bla(CTX-M-15) on plasmids suggests a role in gene expression and/or horizontal transfer.
- Understanding the role of ISEcp1 is crucial for predicting and controlling the spread of CTX-M-15 and similar resistance genes.