BMC MICROBIOLOGY
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2025
·Vol. 25
·期 1
·805
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IF 4.2
Zhou Qianyu,Xue Jinjing,Li Jun,Liu Zhiying,Zou Yinuo,Dai Rui,Gu Kuan,Zhou Yonglin
The advent and global spread of plasmid-carried resistance genes, including the tigecycline resistance gene tet (X3/X4) and the colistin resistance gene mcr-1 , present a substantial threat to public health that requires immediate resolution. This study successfully screened and identified commercial anti-parasitic drugs that efficiently inhibit Tet(X4) enzyme activity (IC 50 = 79.42 µg/mL), revealing that mefloquine exhibited a synergistic antibacterial effect with tetracyclines against tet (X3/X4)-positive bacteria (FIC < 0.5) and an additive effect with tetracyclines against tet (X3/X4)-negative bacteria (0.5 < FIC < 1, excluding minocycline). Molecular dynamics simulations and checkerboard minimum inhibitory concentration (MIC) tests on Tet(X4) mutants in amino acid residues demonstrated that mefloquine’s interaction with the active site of Tet(X4) reduces its activity. The energy contribution of the binding site residues involves PHE221, PHE316, GLY233, PRO315, PHE232, MET212, ALA222 and HIE231, which establish robust interactions with mefloquine (Δ Etotal of ≤ − 0.5 kcal/mol). Moreover, findings from metabonomics, bacterial membrane analysis, ROS detection, NAD + /NADH ratio determination, and intracellular ATP determination indicated that mefloquine may significantly influence bacterial energy metabolism ( P < 0.05). Furthermore, in the mouse infection model of E. coli 47EC, the combination of methacycline and mefloquine, demonstrated significant therapeutic advantages, as evidenced by an increased survival rate (from 20.00% to 80.00%), decreased sepsis score, and decreased bacterial load. Our work is the first to reveal that the commercial medicine mefloquine can prolong the efficacy of tetracycline and treat infections caused by drug-resistant Enterobacteriaceae in clinical environments. Graphical
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SENSORS AND ACTUATORS B-CHEMICAL
·
2023
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IF 8.4
Daxiu Li,Feng Qiu,Ruo Yuan,Yun Xiang
Simultaneous detection and quantification of antimalarial drugs is important for evaluating the spread of their resistance. On the base of the target-induced assembly of branched DNA nanostructure signal amplification and different electrochemical coding tags at distinct potentials, an aptasensing method for multiplexed and highly sensitive detection of piperaquine (PQ) and mefloquine (MQ) antimalarial drugs is established. The target drugs associate with and switch the conformation of the aptamers to release free ssDNA trigger sequences, which initiate the self-assembly of many methylene blue (MB)- and ferrocene (Fc)-labeled auxiliary signal sequences to form branched nano-assemblies on electrode. The electrode-captured MB and Fc tags thus yield highly magnified current reponses at well-resolved potentials for simultaneously monitoring PQ and MQ with respective detection limits as low as 0.061 ng mL −1 (i.e., 0.114 nM) and 0.17 ng mL −1 (i.e., 0.449 nM). Moreover, the simultaneous detection of PQ and MQ in diluted human serum samples has also been verified by the developed sensor, revealing its potential for multiplexed monitoring of different drugs in connection with the corresponding aptamers for various application purposes.
研究领域:
分析化学
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生物化学
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药学
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纳米技术
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TALANTA
·
2025
·
IF 6.1
Tiantian Chen,Qian Xiang,Xuemei Sang,Daxiu Li,Wenjiao zhou,Fengfeng Xu
Malaria remains a significant threat to global health, especially with the emergence of drug-resistant strains. Therefore, precise monitoring of antimalarial drug levels is crucial for assessing and managing drug resistance. Here, we report a multiplex aptasensor that enables simultaneous fluorescence detection of two antimalarial drugs (MQ and PQ) via split dsT7 promoter-mediated transcription of two-color light-up RNA aptamers. The detection mechanism relies on specific binding of target antimalarial drugs (MQ/PQ) to their aptamers, each triggering formation of intact dsT7 promoter to induce amplified transcription of its cognate RNA aptamer. The generated RNA aptamers bind their corresponding organic dyes (TO1-Biotin and MG) with high affinity, yielding 7.7-/25-fold fluorescence enhancement to enable ultrasensitive detection of MQ and PQ with limits of 0.71 ng/mL and 0.069 ng/mL, respectively. The method also exhibits high selectivity and low background signal. Furthermore, this label-free system achieves multiplexed detection of antimalarial drugs in 10-fold diluted human serum (recovery: 98.67–106.84 % for PQ and 99.89–106.19 % for MQ), demonstrating its real utility. This label-free system is adaptable to other biomarkers through aptamer replacement.
研究领域:
生物化学
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分子生物学
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医学诊断
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MICROCHIMICA ACTA
·
2021
·Vol. 189
·期 1
·1-8
·
IF 5.833
Yang Jinlan,Gao Yulan,Yang Li
A novel capillary-based fluorescence microsensor for artemisinin was developed with functional polyoxometalates (POMs) as nanozyme by a layer-by-layer self-assembly strategy. Vanadomolybdophosphoric heteropoly acid ( H 5 PMo 10 V 2 O 40 , PMoV 2 ) and tungstophosphoric heteropoly acid ( Na 5 PW 11 O 39 Cu, PW 11 Cu) with high peroxidase-like activity were synthesized and immobilized on capillary to catalyze artemisinin/thiamine reaction and generate the amplified fluorescence signal. The wide linear range up to 13.0 μM with the low limit of detection of 0.03 μM (S/N = 3) was achieved for the determination of artemisinin by using the proposed POMs-microsensor. The method has been successfully used to detect artemisinin in human plasma and antimalarial drugs with satisfactory accuracy. This work developed a novel capillary fluorescence microsensor with functional POMs as nanozyme, which can serve as a promising candidate in fluorescence microanalysis. Graphical abstract
研究领域:
分析化学
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生物医学工程
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药物分析
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