Chromosomal Amplification of the blaOXA-58 Carbapenemase Gene in a Proteus mirabilis Clinical Isolate
Chromosomal Amplification of the blaOXA-58 Carbapenemase Gene in a Proteus mirabilis Clinical Isolate
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DOI：
10.1128/aac.01697-16
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发表时间：
2017-02-01
影响因子：
4.9
通讯作者：
Naas, Thierry
中科院分区：
文献类型：
--
作者：
Girlich, Delphine;Bonnin, Remy A.;Naas, Thierry
水平基因转移可能发生在关系较远的细菌之间，从而导致遗传可塑性，并在某些情况下获得新的抗性特征。奇异变形杆菌是一种引起人类感染的肠细菌，可能表达各种获得性β-内酰胺抗性基因，包括不同类别的碳青霉烯酶基因。在此，我们报告了一种奇异变形杆菌临床分离株（菌株 1091），其对青霉素（包括替莫西林）具有耐药性，并且对碳青霉烯类药物和广谱头孢菌素的敏感性降低。通过生化测试，在 P. mirabilis 1091 中检测到显着的碳青霉烯水解。由于 PCR 未能检测到肠杆菌科中常见的获得性碳青霉烯酶基因，我们使用全基因组测序方法揭示了 bla(OXA-58) D 类碳青霉烯酶基因的存在，该基因迄今为止仅在不动杆菌属物种中发现。该基因位于与 bla(AmpC) 样基因共存的 3.1 kb 元件上。值得注意的是，这两个基因被推定的 XerC-XerD 结合位点括起来，并插入位于噬菌体的终止酶样小亚基基因和大亚基基因之间的 XerC-XerD 位点。 Southern 印迹显示，两个 bla 基因的表达增加是由于该元件的 6 倍串联扩增所致。这是首次分离产生 OXA-58（一种 D 类碳青霉烯酶）的临床奇异变形杆菌菌株，也是首次描述噬菌体中 XerC-XerD 依赖性抗生素抗性基因的插入。这项研究揭示了 XerC-XerD 重组酶在噬菌体生物学中的新作用。
Horizontal gene transfer may occur between distantly related bacteria, thus leading to genetic plasticity and in some cases to acquisition of novel resistance traits. Proteus mirabilis is an enterobacterial species responsible for human infections that may express various acquired beta-lactam resistance genes, including different classes of carbapenemase genes. Here we report a Proteus mirabilis clinical isolate (strain 1091) displaying resistance to penicillin, including temocillin, together with reduced susceptibility to carbapenems and susceptibility to expanded-spectrum cephalosporins. Using biochemical tests, significant carbapenem hydrolysis was detected in P. mirabilis 1091. Since PCR failed to detect acquired carbapenemase genes commonly found in Enterobacteriaceae, we used a whole- genome sequencing approach that revealed the presence of bla(OXA- 58) class D carbapenemase gene, so far identified only in Acinetobacter species. This gene was located on a 3.1-kb element coharboring a bla(AmpC)- like gene. Remarkably, these two genes were bracketed by putative XerC-XerD binding sites and inserted at a XerC-XerD site located between the terminase-like small- and large-subunit genes of a bacteriophage. Increased expression of the two bla genes resulted from a 6-time tandem amplification of the element as revealed by Southern blotting. This is the first isolation of a clinical P. mirabilis strain producing OXA-58, a class D carbapenemase, and the first description of a XerC-XerD-dependent insertion of antibiotic resistance genes within a bacteriophage. This study revealed a new role for the XerC-XerD recombinase in bacteriophage biology.