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

Abstract

The contribution of the bla OXA-58 gene and its promoter to β-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 bla OXA-58 was the only detected carbapenemase gene. The bla OXA-58 gene was plasmid located, flanked by ISAba3 (downstream) and an ISAba3-like element (upstream). An IS1006 element was inserted into ISAba3-like (IS1006-ΔISAba3-like) to generate a hybrid promoter for bla OXA-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 ΔISAba3-like-bla OXA-58, compared to the same host containing only bla OXA-58. When the fragment was changed from ΔISAba3-like- bla OXA-58 to IS1006-ΔISAba3-like-bla OXA-58, the ATCC 17903 transformant revealed a markedly higher level of bla OXA-58 transcription (12-fold), increased cefuroxime and piperacillin-tazobactam MICs, and homoresistance to imipenem and meropenem. Different roles of the insertion elements preceding the bla OXA-58 gene in Acinetobacter genomic species 13TU are demonstrated. The ISAba3-like-bla OXA-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 bla OXA-58 and mediate homoresistance to carbapenems and also enhanced resistance to piperacillin-tazobactam. Copyright © 2010, American Society for Microbiology. All Rights Reserved.