title: Acquisition of a plasmid-borne blaOXA-58 gene with an upstream IS1008 insertion conferring a high level of carbapenem resistance to Acinetobacter baumannii.
abstract: The oxacillinase gene was reported to confer limited resistance to carbapenem in Acinetobacter baumannii. In this study, we have demonstrated that an A. baumannii clinical isolate harboring a plasmid, pTVICU53, has 11,037 bp encoding 13 open reading frames. A bla(OXA-58) gene with an upstream insertion of truncated ISAba3 (DeltaISAba3) and IS1008 was found in this plasmid. DeltaISAba3and IS1008 provided two independent promoters for the transcription control of the bla(OXA-58) gene. The transformation of pTVICU53 or a shuttle vector bearing IS1008-DeltaISAba3-bla(OXA-58) to different A. baumannii recipients can increase their MICs of carbapenem 64- to 256-fold. The deletion of promoters provided by IS1008 resulted in dramatic decreases in bla(OXA-58) transcription and a 32- to 64-fold reduction in the carbapenem MIC. These findings highlight that A. baumannii might develop carbapenem resistance with a single transformation step, taking up a plasmid containing a genetic construct with a potentially high level of transcription of the bla(OXA-58) gene.
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Te-Li
authors.initials: TL
authors.lastname: Chen
authors.forename: Roy Chen-Chih
authors.initials: RC
authors.lastname: Wu
authors.forename: Men-Fang
authors.initials: MF
authors.lastname: Shaio
authors.forename: Chang-Phone
authors.initials: CP
authors.lastname: Fung
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Cho
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D001483:Base Sequence; D015780:Carbapenems / Q000494:pharmacology*; D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D017931:DNA Primers / Q000235:genetics; D004251:DNA Transposable Elements / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D014170:Transformation, Genetic; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015780:Carbapenems; D017931:DNA Primers; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D001618:beta-Lactamases