novel variant of new delhi metallo-β-lactamase, ndm-20, in escherichia coli

大肠埃希菌中新德里金属-β-内酰胺酶新型变体NDM-20

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2018
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Abstract
The spread of carbapenem-resistant Enterobacteriaceae (CRE) mediated by New Delhi metallo-β-lactamase (NDM) poses a serious challenge to clinicians and has become a major public health concern. NDM has been evolving into variants that possess different hydrolysis activity toward antibiotics, so as to affect treatment strategy. In addition, very few studies on NDM variants have focused on animal-derived bacterial isolates. Our study reports a novel NDM variant, NDM-20, in an isolate of Escherichia coli CCD1 recovered from the food animal swine in China. The isolate that was assigned to ST1114, exhibited high level resistance to all β-lactams tested, including aztreonam and carbapenems. The gene of blaNDM-20 was located on an IncX3-type plasmid, surrounded by multiple insertion sequences. Sequencing analysis demonstrated that blaNDM-20 contained three point mutations at positions 262 (G→T), 460 (A→C), and 809 (G→A), compared with blaNDM-1, and just one point mutation at position 809 (G→A), relative to blaNDM-5. Functional analysis revealed that the blaNDM-20 transformant, DH5α+pHSG398/NDM-20, exhibited a higher resistance to ertapenem than that of blaNDM-1 transformant DH5α+pHSG398/NDM-1. Kinetic parameter analysis showed that NDM-20 had increased enzymatic activity against some penicillins and cephalosporins but decreased carbapenemase activity relative to NDM-5. The identification of NDM-20 further confirms the evolution and prevalence of NDM variants in bacteria of food-animal origin.
由新德里金属-β-内酰胺酶(NDM)介导的耐碳青霉烯类肠杆菌科细菌(CRE)的传播,对临床医生构成了严峻挑战,并已成为一个重大的公共卫生问题。NDM一直在进化出对不同抗生素具有不同水解活性的变体,从而影响治疗策略。此外,关于NDM变体的研究极少关注动物源性细菌分离株。本研究报道了一种新型NDM变体NDM-20,该变体发现于分离自中国食用动物猪的一株大肠埃希菌(*Escherichia coli*)CCD1中。该分离株被鉴定为ST1114型,对所有受试β-内酰胺类抗生素(包括氨曲南和碳青霉烯类)均表现出高水平耐药。*bla*NDM-20基因定位于一个IncX3型质粒上,其周围环绕着多个插入序列。测序分析表明,与*bla*NDM-1相比,*bla*NDM-20在第262位(G→T)、第460位(A→C)和第809位(G→A)存在三个点突变;而与*bla*NDM-5相比,仅在第809位(G→A)存在一个点突变。功能分析表明,*bla*NDM-20转化子DH5α+pHSG398/NDM-20对厄他培南的耐药水平高于*bla*NDM-1转化子DH5α+pHSG398/NDM-1。酶动力学参数分析显示,与NDM-5相比,NDM-20对某些青霉素类和头孢菌素类的酶活性有所增强,但其碳青霉烯酶活性有所减弱。NDM-20的发现进一步证实了NDM变体在食用动物源细菌中的进化与流行。
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Journal journal of magnetic resonance (san diego, calif : 1997)
Year 2018
DOI
10.3389/fmicb.2018.00248
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