MEDICINAL CHEMISTRY RESEARCH
·
2024
·
IF 2.6
Cheng Wenhui,Zhang Yuejuan,Chen Cheng,Gao Lei,Lv Yuwei,Yu Dian,Chen Bin,Wan Yi
The production of carbapenemases is a significant mechanism contributing to carbapenem resistance in Enterobacteriaceae . Among these carbapenemases, OXA-48 presents a distinct challenge and threat, as most β-lactamase inhibitors do not effectively inhibit its activity. In this study, we investigated the inhibitory potential of α-mangostin against OXA-48 with an IC 50 value of 0.52 μM. Enzyme activity assays demonstrated that α-mangostin inhibited OXA-48 reversibly through a non-competitive and dose-dependent inhibition mode. The docking analysis revealed that the 7-hydroxyl group of α-mangostin formed hydrogen bonds with Thr197 and Trp222, whereas the 5-hydroxyl group and the 4-carbonyl group interacted with Lys116 and Met115. Our study indicates that α-mangostin exhibits significant inhibition against OXA-48 and holds promise as a potential compound for the development of β-lactamase inhibitors.
研究领域:
微生物学
·
药理学
·
传染病学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF IMMUNOLOGICAL METHODS
·
2025
·
IF 1.6
Mengying Lun,Yumei Chen,Hongliang Liu,Yanhua Qi,Aiping Wang,Jingming Zhou
The production of carbapenemase is the primary mechanism of bacterial resistance to carbapenem antibiotics. This resistance seriously compromises the efficacy of carbapenem antibiotics in treating infections and poses a significant challenge to clinical anti-infective therapy. Oxacillinase-48 (OXA-48) is a class D carbapenemase, whose genes are usually located on transferable elements and can spread between different strains and genera. Therefore, from the perspective of infection control, effective monitoring and prevention of OXA-48 are imperative. In this study, CdSe/ZnS quantum dots (QDs) were coupled with an anti-OXA-48 monoclonal antibody (mAb) as a fluorescent signal probe to establish a quantum dot-based fluorescent immunochromatographic strip. The test strip contains a Test line (T-line) coated with an anti-OXA-48 monoclonal antibody and a Control line (C-line) coated with Staphylococcus protein A (SPA). Based on a double-antibody sandwich detection mode, it can complete highly sensitive detection of OXA-48 within 10 min. The visual detection limit of this test strip for OXA-48 recombinant protein was 3.13 ng/mL, and there was no cross-reaction with other common carbapenemases (IMP-1, NDM-1, KPC-2, VIM-2, OXA-23). It can be positioned as a rapid and reliable OXA-48 detection tool, providing a novel method for the rapid identification of OXA-48-producing resistant bacterial strains in clinical practice.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Wenyan Jiang,Shan Zhang,Chen Xu,Haojie Sun,Ziye Xing,Xiao Liang,Hongming He,Quanshun Li
The prevalence of antibiotics in natural aquatic environment has become an emerging class of organic pollutants, impacting both aquatic ecosystems and human health. Herein, spherical mesoporous covalent organic frameworks (SMCOF) was successfully synthesized and employed in the immobilization of OXA-48 β-lactamase through pore adsorption, in which 1,3,5-tris(4-aminophenyl)benzene and 2,5-dimethoxyterephthalaldehyde were utilized as the node and linker, respectively. Structural characterization demonstrated that OXA-48 was successfully adsorbed into the pores of SMCOF, achieving a loading capacity of 546.81 mg/g. Meanwhile, OXA-48@SMCOF maintained the catalytic activity of 62.08 % and 104.98 % after the treatment at 50 °C (pH of 7.4) and 37 °C (pH of 11) for 30 min, respectively. Further, all the catalytic activities of OXA-48@SMCOF remained above 88 % after the incubation in the presence of various organic solvents or proteinase K for 1 h. Moreover, OXA-48@SMCOF retained 53.78 % and 41.18 % of original activity after 15 cycles of reuse and 10 days of storage, respectively, indicating its favorable reusability and storage stability. In the application of degrading antibiotics in lake water samples, OXA-48@SMCOF demonstrated superior degradation performance compared to free OXA-48, attributing to the protective effect of SMCOF. Overall, the present study provides a promising technique to construct high performance immobilized enzymes, which is beneficial for the future application of OXA-48@SMCOF in the degradation of antibiotics during water treatment process.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL MICROBIOLOGY
·
2024
·Vol. 62
·期 2
·
IF 6.1
Zhimin Lu,Xiaonan Wang,Licai Ma,Leina Dou,Xiangjun Zhao,Jin Tao,Yang Wang,Shaolin Wang,Dejun Liu,Yingbo Shen,Xuezhi Yu,Wenbo Yu,Liangxi Jia,Zhanhui Wang,Jianzhong Shen,Kai Wen
Rapid phenotypic detection assays, including Carba NP and its variants, are widely applied for clinical diagnosis of carbapenemase-producing Enterobacterales (CPE). However, these tests are based on the acidification of the pH indicator during carbapenem hydrolysis, which limits test sensitivity and speed, especially for the detection of CPE producing low-activity carbapenem (e.g., OXA-48 variants). Herein, we developed a novel rapid and sensitive CPE detection method (Carba PBP) that could measure substrate (meropenem) consumption based on penicillin-binding protein (PBP). Meropenem-specific PBP was used to develop a competitive lateral flow assay (LFA) for meropenem identification. For the detection of carbapenemase activity, meropenem concentration was optimized using a checkerboard assay. The performance of Carba PBP was evaluated and compared with that of Carba NP using a panel of 94 clinical strains characterized by whole-genome sequencing and carbapenem susceptibility test. The limit of detection of PBP-based LFA for meropenem identification was 7 ng mL−1. Using 10 ng mL−1 meropenem as the substrate, Carba PBP and Carba NP could detect 10 ng mL−1 carbapenemase within 25 min and 1,280 ng mL−1 CPE in 2 h, respectively. The sensitivity and specificity were 100% (75/75) and 100% (19/19) for Carba PBP and 85.3% (64/75) and 100% (19/19) for Carba NP, respectively. When compared with Carba NP, Carba PBP showed superior performance in detecting all the tested CPE strains (including OXA-48-like variants) within 25 min and presented two orders of magnitude higher analytical sensitivity, demonstrating potential for clinical diagnosis of CPE.
研究领域:
微生物学
·
临床诊断
·
分子生物学
·
传染病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）