Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli
Bacteria containing bla(NDM-1) gene are a growing threat to almost all clinically β-lactam antibiotics. Especially, the New Delhi metallo-β-lactamase (NDM-1) has become a potential public survival risk. In this study, a novel and efficient strategy for inhibitors and β-lactam antibiotics screening u...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The Royal Society of Chemistry
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078263/ https://www.ncbi.nlm.nih.gov/pubmed/35539612 http://dx.doi.org/10.1039/c7ra12778b |
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author | Wang, Juan Li, Yang Yan, Haizhong Duan, Juan Luo, Xihua Feng, Xueqin Lu, Lanfen Wang, Weijia |
author_facet | Wang, Juan Li, Yang Yan, Haizhong Duan, Juan Luo, Xihua Feng, Xueqin Lu, Lanfen Wang, Weijia |
author_sort | Wang, Juan |
collection | PubMed |
description | Bacteria containing bla(NDM-1) gene are a growing threat to almost all clinically β-lactam antibiotics. Especially, the New Delhi metallo-β-lactamase (NDM-1) has become a potential public survival risk. In this study, a novel and efficient strategy for inhibitors and β-lactam antibiotics screening using recombinant New Delhi metallo-beta-lactamase (NDM-1) was developed. First, the gene of bla(NDM-1) were identified and cloned from multi-drug resistance of Acinetobacter baumannii isolate; by the means of protein expression and purification, recombinant NDM-1 activity was up to 68.5 U ml(−1), and high purity NDM-1 protein with activity of 347.4 U mg(−1) was obtained. Finally, for NDM-1, the inhibitors (aspergillomarasmine A (AMA) and EDTA) with high affinity (HI) and the β-lactam antibiotics (imipenem) with low affinity (LA) were screened out. Surprisingly, the inhibition of the NDM-1 was enhanced by the use of inhibitor combinations (AMA–EDTA (1 : 2)), where the IC(50) of AMA–EDTA was reduced by 88% and 95%, respectively, comparing to the AMA and EDTA alone. More interesting, AMA–EDTA could restore the activity of imipenem when tested against NDM-1 expressing strains (E. coli and Acinetobacter baumannii), with a working time of 120 min and 330 min, respectively. This method is expected to be used in high-throughput screening, drug redesign (including new inhibitors and drugs) and “old drug new use”. |
format | Online Article Text |
id | pubmed-9078263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-90782632022-05-09 Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli Wang, Juan Li, Yang Yan, Haizhong Duan, Juan Luo, Xihua Feng, Xueqin Lu, Lanfen Wang, Weijia RSC Adv Chemistry Bacteria containing bla(NDM-1) gene are a growing threat to almost all clinically β-lactam antibiotics. Especially, the New Delhi metallo-β-lactamase (NDM-1) has become a potential public survival risk. In this study, a novel and efficient strategy for inhibitors and β-lactam antibiotics screening using recombinant New Delhi metallo-beta-lactamase (NDM-1) was developed. First, the gene of bla(NDM-1) were identified and cloned from multi-drug resistance of Acinetobacter baumannii isolate; by the means of protein expression and purification, recombinant NDM-1 activity was up to 68.5 U ml(−1), and high purity NDM-1 protein with activity of 347.4 U mg(−1) was obtained. Finally, for NDM-1, the inhibitors (aspergillomarasmine A (AMA) and EDTA) with high affinity (HI) and the β-lactam antibiotics (imipenem) with low affinity (LA) were screened out. Surprisingly, the inhibition of the NDM-1 was enhanced by the use of inhibitor combinations (AMA–EDTA (1 : 2)), where the IC(50) of AMA–EDTA was reduced by 88% and 95%, respectively, comparing to the AMA and EDTA alone. More interesting, AMA–EDTA could restore the activity of imipenem when tested against NDM-1 expressing strains (E. coli and Acinetobacter baumannii), with a working time of 120 min and 330 min, respectively. This method is expected to be used in high-throughput screening, drug redesign (including new inhibitors and drugs) and “old drug new use”. The Royal Society of Chemistry 2018-02-07 /pmc/articles/PMC9078263/ /pubmed/35539612 http://dx.doi.org/10.1039/c7ra12778b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Wang, Juan Li, Yang Yan, Haizhong Duan, Juan Luo, Xihua Feng, Xueqin Lu, Lanfen Wang, Weijia Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli |
title | Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli |
title_full | Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli |
title_fullStr | Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli |
title_full_unstemmed | Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli |
title_short | Semi-rational screening of the inhibitors and β-lactam antibiotics against the New Delhi metallo-β-lactamase 1 (NDM-1) producing E. coli |
title_sort | semi-rational screening of the inhibitors and β-lactam antibiotics against the new delhi metallo-β-lactamase 1 (ndm-1) producing e. coli |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078263/ https://www.ncbi.nlm.nih.gov/pubmed/35539612 http://dx.doi.org/10.1039/c7ra12778b |
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