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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.

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.

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