Acquisition of a plasmid-borne blaOXA-58 gene with an upstream IS1008 insertion conferring a high level of carbapenem resistance to Acinetobacter baumannii.
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.
Chen
Te-Li
TL
Division of Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Wu
Roy Chen-Chih
RC
Shaio
Men-Fang
MF
Fung
Chang-Phone
CP
Cho
Wen-Long
WL
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
D015780:Carbapenems; D017931:DNA Primers; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D001618:beta-Lactamases