Dataset Information

Novel Variant of New Delhi Metallo-?-lactamase, NDM-20, in Escherichia coli.

ABSTRACT: The spread of carbapenem-resistant Enterobacteriaceae (CRE) mediated by New Delhi metallo-?-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 ?-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, DH5?+pHSG398/NDM-20, exhibited a higher resistance to ertapenem than that of blaNDM-1 transformant DH5?+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.

SUBMITTER: Liu Z

PROVIDER: S-EPMC5826333 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Novel Variant of New Delhi Metallo-β-lactamase, NDM-20, in <i>Escherichia coli</i>.

Liu Zhihai Z Li Jiyun J Wang Xiaoming X Liu Dejun D Ke Yuebin Y Wang Yang Y Shen Jianzhong J

Frontiers in microbiology 20180221

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 <i>Escheri ...[more]

PMID: 29515538

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Project description:The effectiveness of all antibiotics in the β-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-β-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of antibiotics. However, it has been a challenging task to develop broad-spectrum inhibitors of metallo-β-lactamases. Lack of sequence homology across metallo-β-lactamases (MBLs), the rapidly evolving active site of the enzyme, and structural similarities between human enzymes and metallo-β-lactamases, are the primary causes for the difficulty in the development of these inhibitors. Therefore, it is imperative to concentrate on the discovery of an effective NDM-1 inhibitor. This study used various in silico approaches, including molecular docking and molecular dynamics simulations, to investigate the potential of phytochemicals to inhibit the NDM-1 enzyme. For this purpose, a library of about 59,000 phytochemicals was created from the literature and other databases, including FoodB, IMPPAT, and Phenol-Explorer. A physiochemical and pharmacokinetics analysis was performed to determine possible toxicity and mutagenicity of the ligands. Following the virtual screening, phytochemicals were assessed for their binding with NDM-1using docking scores, RMSD values, and other critical parameters. The docking score was determined by selecting the best conformation of the protein-ligand complex. Three phytochemicals, i.e., butein (polyphenol), monodemethylcurcumin (polyphenol), and rosmarinic acid (polyphenol) were identified as result of pharmacokinetics and molecular docking studies. Furthermore, molecular dynamics simulations were performed to determine structural stabilities of the protein-ligand complexes. Monodemethylcurcumin, butein, and rosmarinic acid were identified as potential inhibitors of NDM-1 based on their low RMSD, RMSF, hydrogen bond count, average Coulomb-Schrödinger interaction energy, and Lennard-Jones-Schrödinger interaction energy. The present investigation suggested that these phytochemicals might be promising candidates for future NDM-1 medication development to respond to antibiotic resistance.

Dataset Information

Novel Variant of New Delhi Metallo-?-lactamase, NDM-20, in Escherichia coli.

Publications

Novel Variant of New Delhi Metallo-β-lactamase, NDM-20, in <i>Escherichia coli</i>.

Similar Datasets

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