ISAba1 and Tn6168 acquisition by natural transformation leads to third-generation cephalosporins resistance in Acinetobacter baumannii
ISAba1 and Tn6168 acquisition by natural transformation leads to third-generation cephalosporins resistance in Acinetobacter baumannii
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DOI：
10.1016/j.meegid.2018.05.007
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发表时间：
2018-09-01
影响因子：
3.2
通讯作者：
Da Silva, Gabriela Jorge
中科院分区：
文献类型：
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作者：
Domingues, Sara;Rosario, Natasha;Da Silva, Gabriela Jorge
鲍曼不动杆菌具有内在的β -内酰胺酶基因，即ampC和bla（OXA-51）样基因，只有当ISAba1插入序列位于基因5'端上游时，这些基因才会强烈表达。在一些临床鲍曼不动杆菌菌株中也发现了第二个ampC基因。这些基因表达的增加导致对β -内酰胺类药物的耐药性，包括第三代头孢菌素和/或碳青霉烯类药物。这项工作的目的是评估自然转化参与染色体ampc相关移动元件的转移，以及受体细胞抗性谱的相关变化。以鲍曼不动杆菌A118临床分离株为受体细胞，以耐多药鲍曼不动杆菌Ab51临床分离株为供体DNA来源进行自然转化试验。所有测试的转化子都显示了接近ampC基因的ISAba1的整合。在两个转化子中，isabel通过转位获得并插入到通常的folE和ampC基因之间。其余的转化子获得了第二个ampC基因附近的isabel，作为Tn6168的一部分，可能是通过同源重组获得的。我们的研究表明，自然转化可以促进β -内酰胺耐药性的广泛存在，而非耐药决定因素的获得可以导致鲍曼不动杆菌菌株的敏感性谱的变化。
Acinetobacter baumannii has intrinsic beta-lactamase genes, namely ampC and bla(OXA-51)-like, which are only strongly expressed when the ISAba1 insertion sequence is upstream the 5' end of the genes. A second ampC gene has also been identified in some clinical A. baumannii strains. The increased expression of these genes leads to resistance to beta-lactams, including third-generation cephalosporins and/or carbapenems. The aim of this work was to assess the involvement of natural transformation in the transfer of chromosomal ampC-associated mobile elements, and related changes in the resistance profile of recipient cells. Natural transformation assays with the naturally competent A. baumannii A118 clinical isolate as recipient cell and the multidrug resistant A. baumannii Ab51 clinical isolate as the source of donor DNA produced transformants. All tested transformants showed integration of the ISAba1 close to the ampC gene. In two transformants, the ISAbal was acquired by transposition and inserted between the usual folE and the ampC genes. The remaining transformants acquired the ISAbal adjacent to a second ampC gene, as part of Tn6168, likely by homologous recombination. Our study demonstrates that natural transformation can contribute to the widespread of beta-lactams resistance, and acquisition of non-resistant determinants can lead to changes in the susceptibility profile of A. baumannii strains.