MOLECULES
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2025
·Vol. 30
·期 10
·2122
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IF 4.6
Zhinan Wang,Xiaowei Li,Liang Zhao,Saiwa Liu,Jingjing Du,Xi Jia,Lirui Ge,Jian Xu,Kexin Cui,Yu Ga,Jinxiu Wang,Xi Xia
The emergence ofmcr-1-mediated colistin resistance has become a critical global health concern, highlighting the urgent need for innovative approaches to restore colistin’s therapeutic potential. In this study, we evaluated the antibacterial activity of four matrine-type alkaloids—namely, matrine, oxymatrine, sophocarpine, and sophoramine—againstmcr-1-positiveEscherichia coli. While these alkaloids showed limited efficacy when used alone, the combination of matrine with colistin exhibited remarkable synergistic effects, as demonstrated by checkerboard assays and time-kill curve analyses. The matrine–colistin combination caused minimal erythrocyte damage while effectively attenuating resistance development in vitro. This synergy was further corroborated in a murine infection model, where the combination significantly reduced bacterial loads in target tissues. Mechanistic studies revealed that the matrine–colistin combination enhances antimicrobial activity by disrupting bacterial membrane integrity, increasing intracellular colistin accumulation, and triggering reactive oxygen species-mediated oxidative damage. Collectively, these findings highlight the potential of matrine as a promising adjuvant to overcome colistin resistance, providing a novel therapeutic approach to address the challenge of infections cause by multidrug-resistant Gram-negative bacteria.
研究领域:
微生物学
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药理学
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感染病学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2024
·
IF 4.9
Liang Zhang,Rouying Cai,Yao Wang,Chenfang Miao,Menghan Zhang,Chen Zheng,Jianzhong Zhang,Zhengjun Huang,Shaohuang Weng
Low molecular weight heparin (LMWH) plays an important role in the prevention and treatment of venous thromboembolism. Sensitive and facile monitoring of LMWH is of great significance for clinical special populations. Herein, using enoxaparin (Enox) as the typical representative of LMWH, a convenient and accurate fluorescence method was developed for Enox detection using carbon dots with antioxidant activity (A-CDs) as probe and polymyxin B (PMB) as medium agent. Compared with the simple Enox or PMB, the formed complex of PMB and Enox (PMB-Enox) based on the electrostatic interaction exhibited a new absorbance peak at 340 nm. Correspondingly, the absorbance of PMB-Enox overlapped with the exciting wavelength of A-CDs at 350 nm and effectively quenched the fluorescence of A-CDs through inner filter effect (IFE). The decreased fluorescence intensities of A-CDs were controlled by the increased Enox with constant PMB. A linear fitting equation was obtained between the quenching efficiency (QE) of A-CDs and variable contents of Enox in the range of 0.8–25.0 μg/mL. And the limit of detection (LOD) was 0.64 μg/mL. The recovery of the injection of Enox in human plasma was acceptable with rational relative standard deviations. Moreover, this fluorescence sensing strategy possesses the prospect of developing reliable pharmaceutical analysis method based on the consideration of drug’s property and pharmacological action and the controllable design of fluorescence probes.
研究领域:
医学检验
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药物分析
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生物化学
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DOI
高影响因子
BMC INFECTIOUS DISEASES
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2025
·Vol. 25
·期 1
·1-9
·
IF 3
Ma Ying-Chao,Yang Xiu-Ling,Gu Jian-Jun
ObjectiveTo evaluate the effects of different SARS-CoV-2 inactivation methods on the blood concentration of colistin sulfate.Methods A colistin sulfate reference substance, a quality control plasma sample, and a clinically measured sample were transferred and heated in a 56 °C water batch for 30 min or irradiated under an ultraviolet (UV) lamp for 60 min to examine the stability of the reference solution and quality control plasma sample. Statistical analysis was conducted for the concentration of the clinically measured sample before and after inactivation with the intraclass correlation coefficient (ICC) method, the Passing–Bablok regression, and the Bland–Altman analysis.Results The reference substance of colistin sulfate was unstable under UV inactivation. Under moist heat inactivation, the reference substance and quality control plasma sample of colistin sulfate were stable. The ICC of the concentration results of 27 clinical blood samples with and without moist heat inactivation was 0.995 (P < 0.001). The Passing–Bablok regression equation was Y = 0.01347 + 0.9861X (R2 = 0.994, n = 27). Finally, 96.30% (26/27) of test data was within the 95% limit of agreement. The results obtained with the three statistical analysis methods all showed a high correlation and agreement between the plasma concentration results of samples not inactivated and inactivated with moist heat inactivation.Conclusion The clinical plasma concentration test samples for colistin sulfate can be processed with the moist heat virus inactivation method to reduce the risk of virus infection of medical staff.
研究领域:
医学
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药理学
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病毒学
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DOI
PubMed
高影响因子
RSC Advances
·
2023
·Vol. 13
·期 31
·21537-21544
·
IF 3.9
Xingya Wei,Bangjun Han,Renzheng Gu,Weimin Geng,Naiyun Gao
Disinfection by-products (DBPs) formed in chlorination and chloramination are proved to be cytotoxic and genotoxic and arouse increasing attention. However, previous studies of DBP precursors mainly focused on free amino acids (AAs) and few papers evaluated DBPs' formation potential of combined AAs. This study demonstrated that typical carbonaceous (C-) DBPs, trihalomethanes (THMs) and typical nitrogenous (N-) DBPs, dichloroacetonitrile (DCAN), trichloroacetonitrile (TCAN) and trichloronitromethane (TCNM) could be formed during chlorination and chloramination of polymyxin B sulfate (PBS), a common polypeptide antibiotic working against Gram-negative bacterial infections. The effects of major parameters, including disinfectant dose, contact time, solution pH, temperature, bromide concentration and chloramination mode were evaluated in batch experiments. Different kinds of DBPs exhibited different characteristics as disinfectant dose or contact time increased. Solution pH and temperature affected the formation of DBPs greatly. The formation pathways of different DBPs from chlor(am)ination of PBS were also proposed. Combined AAs, such as PBS, were proved to be important precursors of DBPs during disinfections.
研究领域:
环境科学
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公共卫生
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2025
·
IF 6.7
Shijiong Wei,Dehui Qiu,Xinrong Yan,Bin Liu,Jean-Louis Mergny,David Monchaud,Huangxian Ju,Jun Zhou
Colistin (COL) is a widely used antibiotic and is quite often used as a last-resort treatment option for treating multidrug-resistant Gram-negative bacterial infections. Due to its widespread use, COL accumulates in nature, which represents a novel ecological and health threat. However, there is currently no rapid and specific method available for titrating COL levels in collected samples. Herein, we report a simple chemiluminescence detection method based on the specific interaction between COL and a parallel G-quadruplex (G4). To this end, we exploit the catalytic properties of the G4/hemin DNAzyme, which is able to oxidize substrates to provide a readily monitored readout. The stronger affinity of G4 for COL versus hemin allows for the inactivation of the G4/hemin DNAzyme, which is used herein to quantify COL in solution. Through a series of optimizations, we identified the best G4 sequence (F3TC), oxidation substrate (luminol), and experimental conditions, which allow for the detection of COL over a broad concentration window, from 0.5 to 2,500 ng/mL, with a detection limit of 0.4 ng/mL and excellent selectivity against other antibiotics. Compared with existing methods, the proposed approach provides a simpler and label-free quantification of COL, which might serve as a valuable standard method for antibiotic detection, whose use was validated under real conditions herein.
研究领域:
分析化学
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生物化学
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抗生素检测
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环境监测
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
·
IF 7.5
Chunxia Hu,Jinyong Zhang,Ruiqin Cui,Shiyi Liu,Ying Huang,Huan Zeng,Shumin Cheng,Guibao Zhou,Jingli Li,Longqin Sun,Yan Zhao,Xiao Wang,Jianhua Liu,Quanming Zou,Wei Huang
Given the important role of polymyxin B (PB) in the treatment of drug-resistant Gram-negative bacterial infections, the emergence of PB resistance poses a serious threat to public health. Adjuvant development is a supplementary strategy that can compensate for the lack of novel antibiotics by protecting PB. In this study, we found a small molecule named Lyb24 that showed weak antibacterial activity (minimum inhibitory concentration ≥ 10 μg/ml) but potentiated and revitalized the efficacy of PB against Gram-negative pathogens, including mcr-1 - and mgrB -deletion-mediated PB-resistant strains. Our results showed that Lyb24 inhibits the translational levels of genes associated with the modification of lipid A. In addition, Lyb24 increases the permeability, disrupts the integrity and induces the depolarization of the membrane. We further found that both Lyb24 and PB could directly bind to AzoR and inhibit its activity. Structural analysis showed that Lyb24 binds to the isoalloxazine ring of flavin mononucleotide (FMN) through pi-pi stacking and loop η4 of AzoR. A pneumonia model was used to confirm that the activity against clinical PB-resistant Klebsiella pneumoniae was enhanced due to Lyb24 on PB. In conclusion, we provide a potential therapeutic regimen by combining Lyb24 and PB to treat Gram-negative-resistant bacterial infections. Our findings not only explain the synergistic effect of Lyb24, but also expand our knowledge on the mechanism of action of PB.
研究领域:
微生物学
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药理学
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传染病学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2022
·
IF 7.419
Kaifang Yi,Shuobo Liu,Peiyi Liu,Xingwei Luo,Jinfeng Zhao,Fengbin Yan,Yushan Pan,Jianhua Liu,Yajun Zhai,Gongzheng Hu
It has been recognized that colistin resistance is a growing problem that seriously impairs the clinical efficacy of colistin against bacterial infections. One strategy that has been proven to have therapeutic effect is to overcome the widespread emergence of antibiotic-resistant pathogens by combining existing antibiotics with promising non-antibiotic agents. In this work, antibiotic susceptibility testing, checkerboard assays and time-kill curves were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of the combination. The molecular mechanisms of tetrandrine in combination with colistin were analyzed using fluorometric assay and Real-time PCR. To predict possible interactions between tetrandrine and MCR-1, molecular docking assay was taken. Finally, we evaluated the in vivo efficacy of tetrandrine in combination with colistin against MCR-positive Salmonella . Overall, the combination of tetrandrine and colistin showed significant synergistic activity. In-depth mechanistic analysis showed that the combination of tetrandrine with colistin enhances the membrane-damaging ability of colistin, undermines the functions of proton motive force (PMF) and efflux pumps in MCR-positive bacteria. The results of molecular docking and RT-PCR analyses showed that tetrandrine not only affects the expression of mcr -1 but is also an effective MCR-1 inhibitor. Compared with colistin monotherapy, the combination of tetrandrine with colistin significantly reduced the bacterial load in vivo. Our findings demonstrated that tetrandrine serves as a potential colistin adjuvant against MCR-positive Salmonella .
研究领域:
微生物学
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药理学
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传染病学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
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IF 4.5
Qinyu Luo,Zehua Wu,Yihang Pan,Yan Zhang
Introduction: The discovery of novel antimicrobial mechanisms among existing clinical drugs is urgently needed. Disulfiram, an FDA-approved treatment for alcohol dependence, exhibits broad-spectrum antibacterial effects. However, its mechanism of action remains incompletely understood.Methods: The antimicrobial activity of disulfiram was assessed using bacterial growth curves and colony-forming unit assays. Cytotoxicity was evaluated via propidium iodide staining and flow cytometry. Synergy with polymyxins or kanamycin was examined using checkerboard assays. RNA-seq was performed on disulfiram-treated E. coli, and differentially expressed genes were analyzed using the R package limma. Intracellular reactive oxygen species (ROS) levels were measured with fluorescent probes and flow cytometry.Results: Disulfiram exhibited bacteriostatic, but not bactericidal, effects against E. coli and S. aureus. However, it significantly enhanced the bactericidal activity of colistin or kanamycin, both in vitro and in a murine E. coli infection model. Transcriptomic analysis revealed oxidative stress and zinc-related responses in disulfiram-treated E. coli. The bacteriostatic effects were reversed by the ROS scavenger N-acetyl-l-cysteine and zinc chelators, whereas zinc supplementation enhanced ROS production and growth inhibition.Discussion: This study identifies a zinc-dependent ROS-mediated mechanism underlying the bacteriostatic activity of disulfiram. Although the in vivo concentrations of disulfiram during standard therapy are below its MIC, its synergistic effect with colistin suggests clinical relevance as an adjuvant. Disulfiram-induced redox stress and zinc modulation likely compromise bacterial antioxidant defenses and membrane integrity. These findings support further investigation of dithiocarbamate-based compounds as potential adjuvants or scaffolds for novel antimicrobial development.
研究领域:
微生物学
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药理学
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抗菌研究
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分子生物学
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传染病学
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药物再利用
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产品关联
DOI
PubMed
高影响因子
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