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...

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Autores principales: Wang, Juan, Li, Yang, Yan, Haizhong, Duan, Juan, Luo, Xihua, Feng, Xueqin, Lu, Lanfen, Wang, Weijia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2018
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”.
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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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