Contribution of a Plasmid-Borne bla OXA-58 Gene with Its Hybrid Promoter Provided by IS 1006 and an IS Aba3 -Like Element to β-Lactam Resistance in Acinetobacter Genomic Species 13TU

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Abstract
The contribution of the bla(OXA-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 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-Delta ISAba3-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 Delta ISAba3-like-bla(OXA-58), compared to the same host containing only bla(OXA-58). When the fragment was changed from similar to ISAba3like-bla(OXA-58) to IS1006-Delta ISAba3-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 blaOXA-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.
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