Acquisition of a plasmid-borne blaOXA-58 gene with an upstream IS1008 insertion conferring a high level of carbapenem resistance to Acinetobacter baumannii
Acquisition of a plasmid-borne blaOXA-58 gene with an upstream IS1008 insertion conferring a high level of carbapenem resistance to Acinetobacter baumannii
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DOI：
10.1128/aac.00393-08
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发表时间：
2008-07-01
影响因子：
4.9
通讯作者：
Cho, Wen-Long
中科院分区：
文献类型：
--
作者：
Chen, Te-Li;Wu, Roy Chen-Chih;Cho, Wen-Long
据报道，oxacillinase基因赋予鲍曼不动杆菌对碳青霉烯的有限抗性。在这项研究中，我们已经证明鲍曼不动杆菌临床分离物携带质粒pTVICU53，具有11037 bp编码13个开放阅读框。在该质粒中发现了上游插入截断的ISAba3 （Delta ISAba3）和IS1008的bla（OXA-58）基因。Delta ISAba3和IS1008为bla（OXA-58）基因的转录调控提供了两个独立的启动子。将pTVICU53或携带IS1008-Delta ISAba3-bla（OXA-58）的穿梭载体转化到不同的鲍曼不动杆菌受体，可使其碳青霉烯的mic增加64- 256倍。IS1008提供的启动子缺失导致bla（OXA-58）转录显著降低，碳青霉烯类MIC降低32- 64倍。这些发现表明鲍曼不动杆菌可能通过一个单一的转化步骤产生碳青霉烯抗性，该转化步骤采用了含有bla（OXA-58）基因潜在高水平转录的遗传结构的质粒。
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 (Delta ISAba3) and IS1008 was found in this plasmid. Delta ISAba3 and 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-Delta ISAba3-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.