Contribution of a plasmid-borne blaOXA-58 gene with its hybrid promoter provided by IS1006 and an ISAba3-like element to beta-lactam resistance in acinetobacter genomic species 13TU

Antimicrob Agents Chemother. 2010 Aug;54(8):3107-12. doi: 10.1128/AAC.00128-10. Epub 2010 Jun 1.

Abstract

The contribution of the blaOXA-58 gene and its promoter to beta-lactam resistance has not been validated in Acinetobacter spp. other than Acinetobacter baumannii. We identified a multidrug-resistant (including carbapenem resistance) Acinetobacter genomic species 13TU in which blaOXA-58 was the only detected carbapenemase gene. The blaOXA-58 gene was plasmid located, flanked by ISAba3 (downstream) and an ISAba3-like element (upstream). An IS1006 element was inserted into ISAba3-like (IS1006-DeltaISAba3-like) to generate a hybrid promoter for blaOXA-58, with a -35 promoter located in IS1006 and a -10 promoter in ISAba3-like. The reference strain of Acinetobacter genomic species 13TU, ATCC 17903, revealed higher MICs of amoxicillin, ticarcillin, and piperacillin and heteroresistance to imipenem and meropenem when it was transformed with a shuttle vector containing a fragment encompassing DeltaISAba3-like-blaOXA-58, compared to the same host containing only blaOXA-58. When the fragment was changed from DeltaISAba3-like-blaOXA-58 to IS1006-DeltaISAba3-like-blaOXA-58, the ATCC 17903 transformant revealed a markedly higher level of blaOXA-58 transcription (12-fold), increased cefuroxime and piperacillin-tazobactam MICs, and homoresistance to imipenem and meropenem. Different roles of the insertion elements preceding the blaOXA-58 gene in Acinetobacter genomic species 13TU are demonstrated. The ISAba3-like--blaOXA-58 construct can mediate resistance to penicillin derivatives but only heteroresistance to carbapenems. The insertion of IS1006 into ISAba3-like, generating a hybrid promoter, could further enhance the transcription of blaOXA-58 and mediate homoresistance to carbapenems and also enhanced resistance to piperacillin-tazobactam.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter / classification
  • Acinetobacter / drug effects*
  • Acinetobacter / enzymology
  • Acinetobacter / genetics
  • Anti-Bacterial Agents / pharmacology
  • Carbapenems / pharmacology
  • DNA Transposable Elements / genetics*
  • Drug Resistance, Multiple, Bacterial
  • Genome, Bacterial
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Penicillanic Acid / analogs & derivatives
  • Penicillanic Acid / pharmacology
  • Piperacillin / pharmacology
  • Plasmids / genetics*
  • Promoter Regions, Genetic / genetics*
  • Recombination, Genetic*
  • Sequence Analysis, DNA
  • Species Specificity
  • Tazobactam
  • beta-Lactam Resistance / genetics*
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • DNA Transposable Elements
  • Penicillanic Acid
  • beta-Lactamases
  • Tazobactam
  • Piperacillin

Associated data

  • GENBANK/GU327621