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新德里金属β-内酰胺酶(NDM)的结构、遗传学及全球传播:对公共卫生的威胁

Structure, Genetics and Worldwide Spread of New Delhi Metallo-β-lactamase (NDM): a threat to public health.

作者信息

Khan Asad U, Maryam Lubna, Zarrilli Raffaele

机构信息

Medical Microbiology and Molecular Biology Laboratory, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, 202002, India.

Department of Public Health, University of Napoli Federico II, Italy, Naples, Italy.

出版信息

BMC Microbiol. 2017 Apr 27;17(1):101. doi: 10.1186/s12866-017-1012-8.

DOI:10.1186/s12866-017-1012-8
PMID:28449650
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5408368/
Abstract

BACKGROUND

The emergence of carbapenemase producing bacteria, especially New Delhi metallo-β-lactamase (NDM-1) and its variants, worldwide, has raised amajor public health concern. NDM-1 hydrolyzes a wide range of β-lactam antibiotics, including carbapenems, which are the last resort of antibiotics for the treatment of infections caused by resistant strain of bacteria.

MAIN BODY

In this review, we have discussed bla variants, its genetic analysis including type of specific mutation, origin of country and spread among several type of bacterial species. Wide members of enterobacteriaceae, most commonly Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and gram-negative non-fermenters Pseudomonas spp. and Acinetobacter baumannii were found to carry these markers. Moreover, at least seventeen variants of bla type gene differing into one or two residues of amino acids at distinct positions have been reported so far among different species of bacteria from different countries. The genetic and structural studies of these variants are important to understand the mechanism of antibiotic hydrolysis as well as to design new molecules with inhibitory activity against antibiotics.

CONCLUSION

This review provides a comprehensive view of structural differences among NDM-1 variants, which are a driving force behind their spread across the globe.

摘要

背景

产碳青霉烯酶细菌的出现,尤其是新德里金属β-内酰胺酶(NDM-1)及其变体在全球范围内的出现,引起了重大的公共卫生关注。NDM-1可水解多种β-内酰胺抗生素,包括碳青霉烯类,而碳青霉烯类是治疗耐药菌株引起的感染的最后一道抗生素防线。

正文

在本综述中,我们讨论了bla变体、其遗传分析,包括特定突变类型、起源国家以及在几种细菌物种中的传播情况。发现广泛的肠杆菌科成员,最常见的是大肠杆菌、肺炎克雷伯菌、阴沟肠杆菌,以及革兰氏阴性非发酵菌假单胞菌属和鲍曼不动杆菌携带这些标记。此外,到目前为止,在来自不同国家的不同细菌物种中,已报道了至少十七种bla型基因变体,它们在不同位置的氨基酸上有一到两个残基的差异。对这些变体进行遗传和结构研究,对于理解抗生素水解机制以及设计具有抗生素抑制活性的新分子很重要。

结论

本综述全面介绍了NDM-1变体之间的结构差异,这些差异是它们在全球传播的驱动力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149f/5408368/09a104363db2/12866_2017_1012_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149f/5408368/e8588ded9480/12866_2017_1012_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149f/5408368/cb4d16f203eb/12866_2017_1012_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149f/5408368/09a104363db2/12866_2017_1012_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149f/5408368/e8588ded9480/12866_2017_1012_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149f/5408368/cb4d16f203eb/12866_2017_1012_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/149f/5408368/09a104363db2/12866_2017_1012_Fig3_HTML.jpg

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