Acquisition of a Plasmid Borne bla_OXA-58 Gene with an Upstream IS1008 Insertion Conferring a High Level of Carbapenem Resistance to Acinetobacter baumannii

Division of Infectious Diseases, Department of Internal Medicine, Taipei Veterans General Hospital, Institute of Tropical Medicine, School of Medicine, National Yang-Ming University, Taipei, Division of Clinical Research, Department of Medical Research, Kuang Tien General Hospital, Institute of Clinical Nutrition, Hung Kuang University, Taichung, Taiwan

^* To whom correspondence should be addressed. Email: wenlong{at}ym.edu.tw.

	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 (ISAba3) and IS1008 was found in this plasmid. The ISAba3 and IS1008 provided two independent promoters for the transcription control of bla_OXA-58 gene. Transformation of pTVICU53 or a shuttle vector bearing IS1008-ISAba3-bla_OXA-58 to different A. baumannii recipients can increase their minimal inhibitory concentration (MIC) of carbapenem 64 to 256 fold. Deletion of promoters provided by IS1008 resulted in dramatic decreases of bla_OXA-58 transcription and a 32 to 64-fold reduction of 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 potentially high transcription of bla_OXA-58 gene.