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.
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.
Chen
Te-Li
TL
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, and Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shih-Pai Road, Taipei, 11217, Taiwan.
Chang
Wei-Che
WC
Kuo
Shu-Chen
SC
Lee
Yi-Tzu
YT
Chen
Chien-Pei
CP
Siu
Leung-Kei
LK
Cho
Wen-Long
WL
Fung
Chang-Phone
CP
D000150:Acinetobacter / Q000145:classification / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015780:Carbapenems / Q000494:pharmacology; D004251:DNA Transposable Elements / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial; D016680:Genome, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010397:Penicillanic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D000078142:Tazobactam; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004251:DNA Transposable Elements; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam; D010878:Piperacillin