VETERINARY MICROBIOLOGY
·
2022
·
IF 3.246
Hongyan Luo,Mengru Li,Zhishuang Yang,Dekang Zhu,Pei Li
A novel chromosomally-located β-lactamase gene, bla RASA-1 , was identified in Riemerella anatipestifer RA-CH-1. The RASA-1, encoded by bla RASA-1 , was a class A extended-spectrum β-lactamase (ESBL), which shared 42.7% and 40.5% identities with the RAA-1 and CGA-1 β-lactamase, respectively. Overexpression of RASA-1 in Escherichia coli confers broad resistance to β-lactams and the purified native RASA-1 revealed ESBL-like hydrolysis activity. Blasting in GenBank showed that bla RASA-1 was exclusively detected in Riemerella anatipestifer . Moreover, sequence analysis revealed that this gene was located within the multi-resistance region of Riemerella anatipestifer genome.
研究领域:
微生物学
·
抗药性研究
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DOI
高影响因子
Antibiotics-Basel
·
2025
·Vol. 14
·期 9
·915
·
IF 4.6
Ru Wang,Kun Mi,Aihua Lu,Chengyang Zhang,Lei Sun,Yuxiang Chen,Yuanhu Pan,Yanfei Tao,Lingli Huang
Background/Objectives: Extended-spectrum β-lactamase (ESBL)-producingEscherichia coliposes a significant global health challenge, as it leads to antimicrobial treatment failure and is associated with elevated mortality rates. The use of β-lactam/β-lactamase inhibitor combinations offers an alternative approach for combating ESBL-producing bacteria. Ceftriaxone (CRO) and sulbactam have been coadministered in the clinical settings; however, discrepancies in their pharmacokinetics raise concerns regarding the rationality of this combination.Methods: This study was designed to investigate the postβ-lactamase inhibitor effect (PLIE) under both static and dynamic conditions, with the aim of supporting the clinical application of this combination.Results: The minimum inhibitory concentration (MIC) of CRO/SBT (2:1 ratio) againstE. coliNCTC 13353 was determined to be 32/16 μg/mL. The PLIEs were determined to be −1.26, −0.57, and 0.37 h at CRO/SBT concentrations ranging from 1/2 MIC to 2 MIC, respectively. The results of CRO concentration, β-lactamase activity,blaCTX-M-15expression, and cell morphology collectively support that SBT exerts PLIEs and protects against the antibacterial activity of CRO. In the dynamic hollow-fiber infection model, CRO monotherapy showed no inhibitory effect onE. coli, whereas CRO/SBT combination therapy rapidly eliminated SBT, achieved comparable bactericidal effects, prolonged CRO exposure, and maintained low β-lactamase activity levels.Conclusions: In conclusion, CRO/SBT exerts an inhibitory effect on enzyme-producing strains by being able to produce PLIE to maintain the inhibition of β-lactamase.
研究领域:
微生物学
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感染病学
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药理学
·
临床药学
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抗菌药物治疗
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分子生物学
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转化医学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Optical Materials
·
2023
·
IF 0
Jie Zhu,Yang Sun,Meng-Xin Duan,Zheng-Wu Wang,Xin Tan,Zhen Yu,He-Fang Wang
The fast and accurate detection of β-lactamase is a prerequisite of customized treatments and food safety. We present a pretreatment-free dual-excitation three-mode detection of β-lactamase by using ZnAl2O4:Cr3+ etched by ethylenediaminetetraacetic acid disodium (ZAO-EDTA) as a phosphorescent probe and nitrocefin as the signal mediator. The changes in the wavelength overlaps of UV–vis absorbance of nitrocefin upon interactions with β-lactamase and the dual excitation of ZAO-EDTA enable the design of three detection modes: i.e., the enhanced emission when excited at 393 nm, the quenched emission when excited at 533 nm, and the ratio of enhanced excitation of 393 nm and decreased excitation of 533 nm to determine β-lactamase. All three modes have a wide linear range, high sensitivity and selectivity, and fine anti-interference capability. The lowest limit of detection is observed in the ratiometric excitation mode (0.2 U·L–1), and the proposed method can directly detect β-lactamase in bacteria and milk samples without any pretreatments, with the spiked recoveries of 95.3–113% and relative standard deviation < 3.1%. Therefore, the proposed method would be attractive for the detection of β-lactamase in a complex sample, and the ZAO-EDTA probe can be widely used to establish other excitation ratiometric optosensings by changing other signal mediators.
研究领域:
分析化学
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生物传感
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食品安全
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微生物学
✓ 已验证
DOI
International Journal of Environmental Research and Public Health
·
2013
·Vol. 10
·期 7
·2688-2698
·
IF 1.998
Wenbin Wang,Liqiang Liu,Liguang Xu,Wei Ma,Hua Kuang,Chuanlai Xu
β-Lactamase residues in milk represent a public health risk. The cylinder plate detection method, which is based on bacterial growth, is laborious and time consuming. In this study, 15 monoclonal antibodies (mAbs) were selected against Temoneira (TEM) 1 β-lactamase. A sandwich enzyme-linked immunosorbent assay (ELISA) based on an optimum mAb pair was developed and validated for the detection of β-lactamase. The limit of detection and linear dynamic range of the method were 4.17 ng/mL and 5.5–100 ng/mL, respectively. β-Lactamase recovery in pure milk was 96.82–103.13%. The intra- and inter-assay coefficients of variation were 6.21–7.38% and 12.96–13.74%, respectively. Our developed sandwich ELISA can be used as a rapid detection method of β-lactamase in milk.
研究领域:
食品科学
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免疫学
·
公共卫生
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DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2020
·
IF 3.232
Pan Yu,Jia-Ning Yang,Jin-Wu Yan,Zhi-Zhong Meng,W. David Hong,Adam P. Roberts,Stephen A. Ward,Lei Zhang,Shan Li
The rapid detection of β-lactamases (Blas) and effective screening of Bla inhibitors are critically important and urgent for solving antibiotic resistance and improving precision medicine. Here a novel fluorescent probe CDC-559 was designed and synthesized, which can be used for the selective and direct detection of AmpC Blas. More importantly, it can realize screening the Bla inhibitors with sulbactam sodium and tazobactam as model compounds, and the half-maximal inhibitory concentration are 0.279 μM and 0.053 μM, respectively. CDC-559 can be applied not only to examine the resistance of bacterial strains, but also to categorize its mode of action specifically, which is consistent with the essential result of the Blas. The research suggests that CDC-559 probe has tremendous potential in the rapid detection of AmpC Blas as well as the strains with AmpC-encoded gene, which is instructive in promoting better antibiotic stewardship practices and developments.
研究领域:
化学
·
药理学
·
微生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
FOOD CONTROL
·
2016
·
IF 3.388
Jing Qin,Xiping Cui,Panpan Wu,Zhengyun Jiang,Yingshan Chen,Ruili Yang,Qingqing Hu,Yuanming Sun,Suqing Zhao
Fluorescent sensor assay (FSA) was developed by using a fluorescein-labeled aptamer assembled onto Graphene oxide (GO) in order to determine β-lactamase in milk. Under optimal conditions, FSA indicated a detection range from 1 to 46 U/mL with a limit of detection (LOD) of 0.5 U/mL ( R 2 = 0.999, n = 3). In addition, commercial milk samples tainted with β-lactamase were detected by the established FSA with a recovery rate between 96.04 and 119.67%. Additionally, the reliability and sensitivity of FSA was validated by enzyme-linked immunoassay (ELISA) with a high correlation of 0.993. Thus, these data, combined with the ease and speed of the assay, suggest that the developed FSA may represent a promising method for monitoring β-lactamase contamination in milk.
研究领域:
生物化学
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食品科学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 11
·9288
·
IF 5.6
Lizi Yin,Yuhong Gou,Yuyun Dai,Tao Wang,Kexin Gu,Ting Tang,Sajjad Hussain,Xiaoli Huang,Changliang He,Xiaoxia Liang,Gang Shu,Funeng Xu,Ping Ouyang
In recent years, infections caused by multidrug-resistant (MDR) bacteria have greatly threatened human health and imposed a burden on global public health. To overcome this crisis, there is an urgent need to seek effective alternatives to single antibiotic therapy to circumvent drug resistance and prevent MDR bacteria. According to previous reports, cinnamaldehyde exerts antibacterial activity against drug-resistantSalmonellaspp. This study was conducted to investigate whether cinnamaldehyde has a synergistic effect on antibiotics when used in combination, we found that cinnamaldehyde enhanced the antibacterial activity of ceftriaxone sodium against MDRSalmonellain vitro by significantly reduced the expression of extended-spectrum beta-lactamase, inhibiting the development of drug resistance under ceftriaxone selective pressure in vitro, damaging the cell membrane, and affecting its basic metabolism. In addition, it restored the activity of ceftriaxone sodium against MDRSalmonellain vivo and inhibited peritonitis caused by ceftriaxone resistant strain ofSalmonellain mice. Collectively, these results revealed that cinnamaldehyde can be used as a novel ceftriaxone adjuvant to prevent and treat infections caused by MDRSalmonella, mitigating the possibility of producing further mutant strains.Keywords:cinnamaldehyde;multidrug-resistant bacteria;cell membrane;extended-spectrum beta-lactamase
研究领域:
药理学
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微生物学
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2021
·Vol. 99
·期 2
·362-372
·
IF 2.817
Jia-Zhu Chigan,Jia-Qi Li,Huan-Huan Ding,Yin-Sui Xu,Lu Liu,Cheng Chen,Ke-Wu Yang
Bacterial resistance caused by metallo-β-lactamases (MβLs) has become an emerging public health threat, and the development of MβLs inhibitor is an effective way to overcome the resistance. In this study, thirteen novel O -aryloxycarbonyl hydroxamates were constructed and assayed against MβLs. The obtained molecules specifically inhibited imipenemase-1 (IMP-1) and New Delhi metallo-β-lactamase-1, exhibiting an IC 50 value in the range of 0.10–18.42 and 0.23–22.33 μM, respectively. The hydroxamate 5 was found to be the most potent inhibitor, with an IC 50 of 0.1 and 0.23 μM using meropenem and cefazolin as substrates. ICP-MS analysis showed that 5 did not coordinate to the Zn(II) ions at the active site of IMP-1, while the rapid dilution, thermal shift and MALDI-TOF assays revealed that the hydroxamate formed a covalent bond with the enzyme. Cytotoxicity assays indicated that the hydroxamates have low toxicity in MCF-7 cells. This work provided a potent scaffold for the development of MβLs inhibitors.
研究领域:
微生物学
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药物化学
·
感染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2021
·Vol. 69
·期 12
·1179-1183
·
IF 1.645
Taichi Kamo,Keiichi Kuroda,Shota Kondo,Usaki Hayashi,Satoshi Fudo,Tomoki Yoneda,Akiko Takaya,Michiyoshi Nukaga,Tyuji Hoshino
Metallo-β-lactamases (MBLs) are significant threats to humans because they deteriorate many kinds of β-lactam antibiotics and are key enzymes responsible for multi-drug resistance of bacterial pathogens. As a result of in vitro screening, two compounds were identified as potent inhibitors of two kinds of MBLs: imipenemase (IMP-1) and New Delhi metallo-β-lactamase (NDM-1). The binding structure of one of the identified compounds was clarified by an X-ray crystal analysis in complex with IMP-1, in which two possible binding poses were observed. Molecular dynamics (MD) simulations were performed by building two calculation models from the respective binding poses. The compound was stably bound to the catalytic site during the simulation in one pose. The binding model between NDM-1 and the compound was constructed for MD simulation. Calculation results for NDM-1 were similar to those of IMP-1. The simulation suggested that the binding of the identified inhibitory compound was also durable in the catalytic site of NDM-1. The compound will be a sound basis for the development of the inhibitors for MBLs.
研究领域:
微生物学
·
结构生物学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yue Zhang,Weibiao Wang,Mei Wang,Lijuan Ma,Weiman Zhang,Shuxian Zhang,Gidion Wilson,Zhigang Yang,Yuping Sa,Fen Ma,Xinmin He,Tao Gao,Hui Yuan,Guoning Chen,Xueqin Ma
β-Lactamases (β-LS) are a significant threat to public health due to their role in conferring antibiotic resistance against nearly all clinically used β-lactam antibiotics. Consequently, the search for β-lactamase inhibitors (β-LSI), which can reversibly bind to and inactivate β-LS, has intensified. Here, a sensitive and rapid cellulose-based colorimetric sensor integrated with affinity identification model was designed for high-throughput screening of β-LSI. The innovative concept of a nitrocefin-based colorimetric paper sensor strategy was effective in rapidly detecting the inhibitory effects of herbals on β-LS. Then, potential β-LSI present in the screened herbals were captured, separated, and identified utilizing affinity identification model. The efficacy of the developed method was validated with both negative and positive drugs and was subsequently applied to the screening of β-LSI in 7 different herbal samples. Notably, Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou exhibited significant β-LS inhibitory activity. Further affinity separation and LC-MS analyses identified 2 bioactive compounds, spinosin, and magnoflorine, as the agents responsible for this inhibitory effect, with IC 50 values of 143.53 μM and 294.66 μM, respectively. The inhibitory effects and mechanisms were validated through antibacterial activity testing, molecular docking, and dynamic simulation. Notably, spinosin combined with aztreonam showed greater antibacterial effectiveness than avibactam. This study not only establishes a platform for the effective preliminary screening of β-LSI as a potential antimicrobial resistance-reversing agent for future clinical applications, but also inspires the further development of other cellulose-based colorimetric sensors for the rapid and high-throughput discovery of various enzyme inhibitors in complex natural medicines.
研究领域:
微生物学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
BIOSCIENCE REPORTS
·
2018
·Vol. 38
·期 2
·
IF 2.899
Wang Qian,He Yuan,Lu Rui,Wang Wen-Ming,Yang Ke-Wu,Fan Hai Ming,Jin Yi,Blackburn G. Michael
The New Delhi metallo-β-lactamase (NDM-1) is an important clinical target for antimicrobial research, but there are insufficient clinically useful inhibitors and the details of NDM-1 enzyme catalysis remain unclear. The aim of this work is to provide a thermodynamic profile of NDM-1 catalysed hydrolysis of β-lactams using an isothermal titration calorimetry (ITC) approach and to apply this new method to the identification of new low-molecular-weight dicarboxylic acid inhibitors. The results reveal that hydrolysis of penicillin G and imipenem by NDM-1 share the same thermodynamic features with a significant intrinsic enthalpy change and the release of one proton into solution, while NDM-1 hydrolysis of cefazolin exhibits a different mechanism with a smaller enthalpy change and the release of two protons. The inhibitory constants of four carboxylic acids are found to be in the micromolar range. The compounds pyridine-2,6-dicarboxylic acid and thiazolidine-2,4-dicarboxylic acid show the best inhibitory potency and are confirmed to inhibit NDM-1 using a clinical strain of Escherichia coli. The pyridine compound is further shown to restore the susceptibility of this E. coli strain to imipenem, at an inhibitor concentration of 400 μM, while the thiazoline compound also shows a synergistic effect with imipenem. These results provide valuable information to enrich current understanding on the catalytic mechanism of NDM-1 and to aid the future optimisation of β-lactamase inhibitors based on these scaffolds to tackle the problem of antibiotic resistance.
研究领域:
微生物学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2015
·Vol. 7
·期 11
·4602-4607
·
IF 1.821
MingHui Li,WenShen He,LiJun Zhang,ChengLi Duan
A capillary zone electrophoresis method was established for simultaneous analysis of penicillin G and penicillin acid in milk. Milk samples were deproteinized and the analytes were extracted with acetonitrile. Separation of target compounds was performed through electrophoresis. Under optimum conditions, the proposed method demonstrated good correlation coefficients (R > 0.9953), precision (<6.2%), accuracy (89.2–96.8%), and limits of detection and quantification of penicillin G and penicillin acid (LOD, 0.01 and 0.5 μg mL−1, LOQ, 0.04 to 1.7 μg mL−1, respectively). The proposed method for the determination of penicillin and penicillin acid in milk is rapid, convenient and low-cost, and can measure β-lactamase activity in milk. The thermal stabilities of penicillin G, penicillin acid, and β-lactamases in milk were satisfactory when the temperature was lower than 303 K. When the temperature was higher than 353 K for 5 h, β-lactamase tended to be inactivated completely. When the temperature was 373 K, penicillin G and penicillin acid were easily degraded.
研究领域:
分析化学
·
食品科学
·
微生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）