A Clinical Extensively-Drug Resistant (XDR) Escherichia coli and Role of Its β-Lactamase Genes.
A Clinical Extensively-Drug Resistant (XDR) Escherichia coli and Role of Its β-Lactamase Genes.
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DOI：
10.3389/fmicb.2020.590357
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发表时间：
2020
影响因子：
5.2
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Wang M;Wang W;Niu Y;Liu T;Li L;Zhang M;Li Z;Su W;Liu F;Zhang X;Xu H
从患者尿样中分离到一株广泛耐药（XDR）大肠埃希菌W60。研究了其XDR表型的遗传基础，特别是其对β-内酰胺/BLI（β-内酰胺酶抑制剂）组合的耐药性基础。确定XDR表型后，进行第三代基因组测序以鉴定E. coli W60。进行进一步的克隆分析以鉴定β-内酰胺/BLI组合抗性的决定因素。结果表明，E.大肠杆菌W60对几乎所有测试的抗生素都有抗性，包括所有常用的β-内酰胺/BLI组合。对E. coliW60中发现了两个新的可转移质粒。进一步的遗传分析显示blaNDM-5导致对β-内酰胺/BLI组合的高抗性，这通过共表达bleMBL而增强。pECW602具有截短的blaTEM，其由于N-末端信号肽编码区的缺失而不具有功能。本研究得出了几个重要结论：E.大肠杆菌W60的耐药主要是由于存在可转移的多药耐药质粒; NDM-5对β-内酰胺/BLI组合具有高耐药性; bleMBL的共表达增强了NDM-5引起的耐药性; TEM型β-内酰胺酶的信号肽对其分泌和功能至关重要。本研究的结果显示了可转移的多药耐药质粒和金属β-内酰胺酶的危险性，这两者在多药耐药病原体的分析和治疗中应给予更多的关注。
An extensively-drug resistant (XDR) Escherichia coli W60 was isolated from the urine sample of a patient. The genetic basis for its XDR phenotype was investigated, particularly the basis for its resistance toward β-lactam/BLI (β-Lactamase Inhibitor) combinations. Following determination of the XDR phenotype, third generation genomic sequencing was performed to identify genetic structures in E. coli W60. Further cloning analysis was performed to identify determinants of β-lactam/BLI combination resistance. It was found that E. coli W60 is resistant to nearly all of the tested antibiotics including all commonly used β-lactam/BLI combinations. Analysis of the genomic structures in E. coli W60 showed two novel transferable plasmids are responsible for the resistance phenotypes. Further genetic analysis showed blaNDM–5 leads to high resistance to β-lactam/BLI combinations, which was enhanced by co-expressing bleMBL. pECW602 harbors a truncated blaTEM that is not functional due to the loss of the N-terminal signal peptide coding region. Research performed in this work leads to several significant conclusions: the XDR phenotype of E. coli W60 can be attributed to the presence of transferable multidrug resistance plasmids; NDM-5 confers high resistance to β-lactam/BLI combinations; co-expression of bleMBL enhances resistance caused by NDM-5; the signal peptides of TEM type β-lactamases are essential for their secretion and function. Findings of this work show the danger of transferable multidrug resistance plasmids and metallo-β-lactamases, both of which should be given more attention in the analysis and treatment of multidrug resistant pathogens.
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影响因子：
3.2
作者：
Karaiskos I;Giamarellou H
通讯作者：
Giamarellou H
影响因子：
--
作者：
Adamczuk M;Zaleski P;Dziewit L;Wolinowska R;Nieckarz M;Wawrzyniak P;Kieryl P;Plucienniczak A;Bartosik D
通讯作者：
Bartosik D
影响因子：
4.9
作者：
Dortet, Laurent;Nordmann, Patrice;Poirel, Laurent
通讯作者：
Poirel, Laurent
影响因子：
4.9
作者：
Jeong, Seri;Kim, Jung Ok;Jeong, Seok Hoon
通讯作者：
Jeong, Seok Hoon
影响因子：
10.7
作者：
Kumar, Sudhir;Stecher, Glen;Tamura, Koichiro
通讯作者：
Tamura, Koichiro