摘要

水平基因转移可能发生在远端相关细菌之间，从而导致遗传可塑性，并且在某些情况下导致获得新的抗性性状。奇异变形杆菌是负责人类感染的肠内细菌物种，其可表达各种获得性β-内酰胺抗性基因，包括不同种类的碳青霉烯酶基因。在这里，我们报告了显示青霉素耐药的变形杆菌临床分离株（菌株1091），包括替莫西林，以及降低的碳青霉烯类敏感性和对扩展频谱头孢菌素的敏感性。使用生物化学测试，在奇异变形杆菌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blaOXA-58D类碳青霉烯酶基因的存在仅在不动杆菌属中才被鉴定。该基因位于与blaAmpC样基因共同作用的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和大亚基基因之间的XerC-XerD位点。通过Southern印迹显示，两个bla基因的表达增加是由元件的6次串联扩增引起的。这是产生OXA-58，D类碳青霉烯酶的临床奇异变形杆菌菌株的首次分离，以及在噬菌体内首次描述了XerC-XerD依赖性插入抗生素抗性基因。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 β-lactam resistance genes, including different classes of carbapenemase genes. Here we report a Proteus mirabilisclinical 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 blaOXA-58 class D carbapenemase gene, so far identified only in Acinetobacter species. This gene was located on a 3.1-kb element coharboring a blaAmpC-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.

http://aac.asm.org/content/61/2/e01697-16.short