Genetic structure associated with blaOXA-18, encoding a clavulanic acid-inhibited extended-spectrum oxacillinase

Thierry Naas1, Fatemeh Namdari, Pierre Bogaerts

  • 1Service de Bactériologie-Virologie, INSERM U914, Hôpital de Bicêtre, Le Kremlin-Bicêtre Cedex, France. thierry.naas@bct.aphp.fr

Insights

The bla(OXA-18) gene, encoding a clavulanic acid-inhibitable extended-spectrum beta-lactamase, was mobilized by a novel insertion sequence ISCR19 in Pseudomonas aeruginosa. This study suggests the spread of oxacillin-type beta-lactamases in a Belgian hospital.

Area of Science:

  • Microbiology
  • Genetics
  • Molecular Biology

Background:

  • Extended-spectrum beta-lactamases (ESBLs) are a growing public health concern.
  • OXA-type beta-lactamases are a significant class of ESBLs, with OXA-18 being a notable example.
  • Understanding the genetic environment of antibiotic resistance genes is crucial for tracking their spread.

Purpose of the Study:

  • To determine the genetic environment of the bla(OXA-18) gene in a Pseudomonas aeruginosa clinical isolate.
  • To investigate the mechanism of bla(OXA-18) gene mobilization.
  • To assess the presence and spread of bla(OXA-18) and bla(OXA-20) in clinical isolates at a Belgian hospital.

Main Methods:

  • Cloning of an 8.2-kb genomic DNA fragment containing bla(OXA-18) from P. aeruginosa MUS.
  • Characterization of the genetic elements flanking bla(OXA-18), including insertion sequences and gene cassettes.
  • Polymerase chain reaction (PCR) and pulsed-field gel electrophoresis (PFGE) to analyze clinical isolates.

Main Results:

  • The bla(OXA-18) gene was found to be bracketed by two duplicated ISCR19 insertion sequences, lacking typical integron features.
  • A novel mobilization mechanism involving ISCR19, a truncated integrase, and a truncated gene cassette was proposed.
  • The bla(OXA-20) gene was also identified within the same genetic structure.
  • Three P. aeruginosa clinical isolates from different wards carried identical bla(OXA-18)/bla(OXA-20) genetic structures, suggesting clonal spread.

Conclusions:

  • ISCR19 likely mediated the mobilization of the bla(OXA-18) gene through rolling-circle transposition and homologous recombination.
  • The study identified the genetic elements responsible for bla(OXA-18) mobilization in P. aeruginosa.
  • The findings suggest the dissemination of oxacillin-type ESBLs in P. aeruginosa at Saint-Luc University hospital in Brussels, Belgium.

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