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
·
感染病学
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药理学
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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
Research
·
2025
·
IF 10.7
Lei Xu,Sangyu Hu,Yuzhu Pei,Yutong Zhou,Xiuli Zhang,Linlin Ding,Minhe Cui,Yonglin Zhou,Xuming Deng,Zihao Teng,Jianfeng Wang
The emergence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) severely compromises conventional β-lactam antibiotics efficacy and poses an extensive global health challenge. Given the close relationship between docosahexaenoic acid (DHA) and metabolic alterations, this study aimed to reveal the novel function of DHA to potentiate β-lactam antibiotics activity through a lipid peroxidation mechanism. Additionally, DHA exhibited significant inhibitory effects on the catalytic function of β-lactamase through interactions with active residues. Herein, the dual-faceted mechanisms of perturbation of lipid metabolism and β-lactamase catalytic inhibition achieved the potentiated antibacterial efficacy of β-lactam antibiotics in combination with DHA against MRSA. Furthermore, to enhance the pharmacodynamic performance and stability of DHA, amoxicillin and DHA co-loaded nanoemulsions (Amo/DHA-NEs) were prepared via high-energy emulsification. Intriguingly, we found that Amo/DHA-NEs effectively rescued MRSA-induced infections in the murine infection models, as evidenced by the superior bacterial clearance and mitigated inflammation. Collectively, this work reveals a potentially exploitable link between DHA-driven metabolic reprogramming and β-lactams resistance, and we propose combination therapies of DHA and β-lactams targeting the emerging threat of MRSA infections.
研究领域:
微生物学
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药理学
·
感染病学
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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
·
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
·
免疫学
·
公共卫生
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DOI
高影响因子
POLYMERS FOR ADVANCED TECHNOLOGIES
·
2022
·Vol. 33
·期 12
·4120-4130
·
IF 3.348
Xue Meng,Da Zhang,Meng Wang,Ronghui Zhao,Pengfei Zhang,Jingyuan Zhao,Kuilin Deng
For the nontraditional aggregation-induced emission (AIE) active polymers, the heterocyclic structure on the macromolecular backbone and side chains play a crucial role in its fluorescence generation. In this paper, we facilely prepared a series of poly(β-lactam) derivatives (PLTM) by Staudinger polymerization. As expected, PLTMs with four-membered heterocycles along the main-chain shows a remarkable AIE performance with the fluorescence emission at 520 nm, while no fluorescence was observed for both β-lactam (repeating unit) and a model polymer for PLTM. The fluorescence properties of PLTMs greatly depend on the intramolecular aggregation of β-lactam structures, the size of the substituents, and appropriate length of CH 2 spacer. In addition, PLTMs can specifically detect Fe 3+ ions with a limit of detection (LOD) of 7.2 μM even in the presence of other 13 metal ions. Similar to the biological activity of β-lactam, AIE-active PLTMs shows a bactericidal effect on Staphylococcus aureus and Escherichia coli with the minimum inhibitory concentration of about 8 and 4 mg/mL. In brief, the preparation and versatility of PLTMs with β-lactam structure provide useful references for designing other nontraditional AIE-active polymers as well as for ion detection and antibacterial processes.
研究领域:
高分子化学
·
分析化学
·
生物化学
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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
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DOI
PubMed
高影响因子
Materials Today Communications
·
2022
·
IF 3.662
Deyan Gong,Xiang Huang,Zineng Yi,Qianpeng Zhou,Xiaona Xu,Xiaohan Meng,Congyu Liu,Zhaohua Miao,Zhengbao Zha
As a metabolite or reductive cytoprotective gas of bacteria to mediate and mitigate the oxidative stress imposed by antibiotics, hydrogen sulfide (H 2 S) related drug-resistant mechanisms represent a growing point in bacteria drug-resistant research. Thereby, novel diagnostic strategies exploration for H 2 S related drug-resistant pathways recognition are important for drug-resistant bacteria monitoring. Herein, a new organic fluorescent dye ( E )− 3-(3,3-dimethyl-2-styryl-3 H -benzo[ f ]indol-1-ium-1-yl) propane-1-sulfonate self-assembled nanoprobe (DPS NP, ~200 nm) was designed for ratiometric fluorescent monitoring the change of H 2 S concentration. DPS NP exhibited ratiometric fluorescence alteration from yellow (λ em = 553 nm) to blue (λ em = 464 nm) due to nucleophilic addition reaction with H 2 S within five minutes. DPS NP exhibits remarkable capabilities with selectively sensitive colorimetric and ratiometric fluorescent alteration toward H 2 S over other analytes. Fluorescence microscopy imaging or ratiometric fluorescent visualization for monitoring the concentration of bacterial released H 2 S show DPS NP can act as particular diagnostic technique for screening of β -lactam antibiotic resistance in Methicillin-resistant Staphylococcus aureus (MRSA) and nonresistant bacteria Staphylococcus aureus ( S. aureus ) .
研究领域:
微生物学
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医学诊断
·
化学传感
✓ 已验证
DOI
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
·
食品科学
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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
·
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
·
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
危险品化学品经营许可证（带存储）