Disruption of the blaOXA-51-like gene by ISAba16 and activation of the blaOXA-58 gene leading to carbapenem resistance in Acinetobacter baumannii Ab244

J Antimicrob Chemother. 2012 Jan;67(1):59-63. doi: 10.1093/jac/dkr415. Epub 2011 Oct 5.

Abstract

Objectives: This study examines the mechanism of carbapenem resistance in Acinetobacter baumannii isolate Ab244.

Methods: A multiplex PCR for the detection of the bla(OXA-23-like), bla(OXA-40-like), bla(OXA-51-like) and bla(OXA-58-like) families was performed. MICs of imipenem and meropenem were determined by the agar dilution method. The sequence surrounding the bla(OXA-132) gene was determined by amplification with primer pairs encompassing a part of fxsA and an acetyltransferase gene (GNAT). The sequence upstream of the bla(OXA-58) gene was determined by sequencing. SDS-PAGE and carO PCR were performed to check the integrity of the outer membrane proteins. RT-PCRs for the expression of the bla(OXA-132) gene and the bla(OXA-58) gene were performed.

Results: Isolate Ab244 harboured bla(OXA-132) belonging to the bla(OXA-51-like) gene cluster and a bla(OXA-58) gene. The 4239 bp region between fxsA and GNAT showed an insert of ISAba16 (where IS stands for insertion sequence) after the first 15 nucleotides of the bla(OXA-132) gene, with an 8 bp target site duplication at the 5' and 3' ends of ISAba16. The sequence oriented in the 5'→3' direction caused insertional inactivation of the bla(OXA-132) gene. The bla(OXA-58) gene was highly expressed by the promoters provided by an ISAba3-like structure found upstream of the gene. The isolate was resistant to meropenem and had intermediate resistance to imipenem, and was also positive for ISAba1.

Conclusions: This is the first report showing ISAba16-mediated inactivation of the bla(OXA-132) gene in strain Ab244. The resistance to carbapenems in strain Ab244 is related to the acquisition of the bla(OXA-58) gene, here governed by an ISAba3-like element.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / drug effects
  • Acinetobacter baumannii / enzymology*
  • Acinetobacter baumannii / genetics
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / analysis
  • Carbapenems / pharmacology*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • Electrophoresis, Polyacrylamide Gel
  • Gene Expression Profiling
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Multiplex Polymerase Chain Reaction
  • Mutagenesis, Insertional*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • beta-Lactam Resistance*
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Carbapenems
  • DNA, Bacterial
  • beta-Lactamases

Associated data

  • GENBANK/JN415682