Nanoscale
·
2019
·Vol. 11
·期 19
·9468-9477
·
IF 6.97
Xu Zhang,Lizhi Liu,Lunjie Huang,Wentao Zhang,Rong Wang,Tianli Yue,Jing Sun,Guoliang Li,Jianlong Wang
Numerous infectious diseases that cause clinical failures and relapses after antibiotic therapy have been confirmed to be induced by pathogenic intracellular bacteria. The existing therapeutic strategies fail to eliminate intracellular bacteria mainly due to a guard reservoir provided by the cell membrane, which can deactivate antibiotics. Herein, we have reported the design of a pH-responsive metal organic framework (MOF)/antibiotic synergistic system for the targeted highly efficient elimination of intracellular bacteria. The obtained tetracycline (Tet)@ZIF-8@ hyaluronic acid (HA) system (abbreviated to TZH) can be taken up by cells owing to the presence of CD44 receptors on the cell surface via an HA-mediated pathway. Zinc ions and antibiotics, released from TZH under acidic conditions caused by bacteria, have a synergistic antibacterial effect both in vitro and in vivo. The clearance rate of TZH to the intracellular bacteria reached over 98% within the limits of biotoxicity, which indicated that this delivery system can pass the cell membrane “barriers” and restore the efficacy of endangered antibiotics. This synergistic strategy shows potential in optimizing the efficacy-dosage correlation of antibiotics for related infection treatments and constructing versatile controlled release delivery systems for a broad range of applications.
研究领域:
药学
·
生物医学工程
·
传染病学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Boru Gao,Mengmeng Dou,Jin Wang,Shuming Li,Dongying Wang,Lin Ci,Yao Fu
Contaminants such as antibiotics and the resulting antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) have become a hot topic in the field of wastewater purification. In this study, a method was proposed to simultaneously remove antibiotics and reduce ARB and ARGs with C–(N) 3 defect carbon nitride-coupled persulfates (CN-C V2 /PS). The location of the C–(N) 3 defects was determined by a combination of spectroscopic techniques and electron spin resonance tests. Based on photoluminescence and electrochemical tests, and deformation charge density calculations, electron traps were generated at defect sites resulting in enhanced electron–hole separation. The mineralization rates of CN-C V2 /PS for six typical antibiotics were 11–17% and 21–28% higher than those of CN-C V2 and conventional CN , respectively. Over the same reaction time, the inactivation rates of CN-C V2 /PS for E. coli and E. faecalis screened from wastewater treatment plants were 3.6 and 2.7 log higher than that of CN-C V2 . In addition, CN-C V2 /PS showed a reduction rate of more than 2.5 log for tet A and intI 1. DFT calculation showed that due to the formation of defects, the adsorption energy between the PS and catalysts increased from –8.924 eV (CN) to –18.340 eV (CN-C V2 ). At the same time, the effective stretch of peroxide bond of PS changed from 1.505 Å to 1.519 Å. Both results indicated that the activation of PS was significantly enhanced in the presence of the modified CN-C V2 . The synergetic effect of CN-C V2 /PS is expected to remove the antibiotics, resistant bacteria and genes efficiently in future wastewater advanced treatment.
研究领域:
环境科学
·
化学工程
·
材料科学
·
废水处理
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DOI
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2014
·Vol. 22
·期 6
·4587-4596
·
IF 2.757
Li Jianan,Cheng Weixiao,Xu Like,Strong P. J.,Chen Hong
In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet , 2 sul ), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene ( intI 1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8 % tetracyclines, 66.8 % sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI 1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria ( R
2 = 0.330, P < 0.05), there was no significant correlation between antibiotics and the corresponding resistant bacteria ( P > 0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes ( P < 0.05). Tet (A) and tet (B) displayed noticeable relationships with both tetracycline and combined antibiotic-resistant bacteria ( P < 0.01).
研究领域:
环境科学
·
微生物学
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公共卫生
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-18
·
IF 15.7
Fang Dan,Xu Tianqi,Li Fulei,Sun Yue,Sun Jingyi,Yin Yanqing,Zhang Haijie,Wang Zhiqiang,Liu Yuan
Tigecycline is a last-resort antibiotic to treat complicated infections caused by multidrug-resistant pathogens, while the emergence of plasmid-mediated tet (X) family severely compromises its clinical efficacy. Novel antimicrobial strategies not limited to new antibiotics in pharmaceutical pipeline are urgently needed. Herein, we reveal the metabolic disparities between tet (X)-negative and -positive E. coli , including distinct energy demand patterns under tigecycline exposure. In particular, the cysteine and methionine metabolism pathway is remarkably downregulated in tet (X)-positive bacteria. More importantly, we find that the addition of exogenous L-methionine (Met) effectively resensitizes tet (X)-positive pathogens to tigecycline. Our mechanistic analysis demonstrates that exogenous Met promotes intracellular tigecycline accumulation by upregulating bacterial proton motive force. Moreover, Met accelerates the conversion to S-adenosyl-L-methionine, an essential methyl donor, thereby enhancing 5mC methylation modification in the promoter region of tet (X4) gene and reducing its expression. Consistently, the potentiation of Met to tigecycline is abolished in tet (X4)-carrying E. coli Δ dcm but restored in dcm -complementary bacteria, which encodes DNA-cytosine methyltransferase. In multiple animal models of infection, Met markedly potentiates the effectiveness of tigecycline against pathogenic E. coli and K. pneumoniae . Overall, this work highlights the therapeutic potential of Met in overcoming plasmid-mediated high-level tigecycline resistance, and provides a new paradigm to enhance antibiotic efficacy by harnessing cellular metabolic networks as well as epigenetic modifications.
研究领域:
微生物学
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药理学
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分子生物学
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传染病学
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代谢工程
✓ 已验证
DOI
PubMed
高影响因子
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