Communications Biology
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2020
·Vol. 3
·期 1
·1-10
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IF 4.165
Liu Yuan,Jia Yuqian,Yang Kangni,Li Ruichao,Xiao Xia,Wang Zhiqiang
Recent emergence of high-level tigecycline resistance mediated by Tet(X3/X4) in Enterobacteriaceae undoubtably constitutes a serious threat for public health worldwide. Antibiotic adjuvant strategy makes antibiotic more effective against these resistant pathogens through interfering intrinsic resistance mechanisms or enhancing antibiotic actions. Herein, we screened a collection of drugs to identify compounds that are able to restore tigecycline activity against resistant pathogens. Encouragingly, we discovered that anti-HIV agent azidothymidine dramatically potentiates tigecycline activity against clinically resistant bacteria. Meanwhile, addition of azidothymidine prevents the evolution of tigecycline resistance in E. coli and the naturally occurring horizontal transfer of tet (X4). Evidence demonstrated that azidothymidine specifically inhibits DNA synthesis and suppresses resistance enzyme activity. Moreover, in in vivo infection models by Tet(X4)-expression E. coli , the combination of azidothymidine and tigecycline achieved remarkable treatment benefits including increased survival and decreased bacterial burden. These findings provide an effective regimen to treat infections caused by tigecycline-resistant Escherichia coli .
研究领域:
微生物学
·
感染病学
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药理学
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DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2023
·
IF 3.3
Yumeng Cheng,Yakun Li,Meng Yang,Yang He,Xinru Shi,Zhidan Zhang,Yesheng Zhong,Yuan Zhang,Hongbin Si
Antibiotic-resistant bacteria are emerging all the time, but the continued emergence of novel resistance genes and genetic structures is even more alarming. Tigecycline is currently the important last barrier in the treatment of multidrug-resistant (MDR) infections. tet (X), a resistance gene to tigecycline, is the most prevalent and constantly emerging novel variants. In this research, we characterized two MDR Acinetobacter indicus strains to tigecycline that were identified and analyzed by antimicrobial susceptibility testing, conjugation transfer, whole genome sequencing (WGS) and bioinformatics analysis, and gene function analysis. The results showed that three tet (X) variants were carried in BDT201, including tet (X6) on the chromosome, tet (X3) on the plasmid pBDT201–2, and a novel tet (X5) variant adjacent to the IS Aba1 elements on the plasmid pBDT201–3. The novel Tet(X5) variant showed 98.7% amino acid identity with Tet(X5) and was named Tet(X5.4). By expressing tet (X5.4) gene, the tigecycline minimum inhibitory concentration (MIC) values for Escherichia coli JM109 increased 32- fold (from 0.13 to 4 mg/L). BDT2076 contained tigecycline and carbapenems resistance genes, such as tet (X3), bla OXA-58 , bla NDM-3 , and bla CARB-2 . The continuous emergence of MDR bacteria and resistance genes is a global environmental health issue that can not be ignored and therefore needs to pay more urgent attention to it.
研究领域:
微生物学
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分子生物学
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抗生素研究
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环境健康
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DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2023
·
IF 13.6
Xiuli Chen,Yanchu Ke,Ying Zhu,Mingbang Xu,Chao Chen,Shuguang Xie
Tetracycline (TC) is an antibiotic that is recently found as an emerging pollutant with low biodegradability . Biodegradation shows great potential for TC dissipation. In this study, two TC-degrading microbial consortia (named SL and SI) were respectively enriched from activated sludge and soil. Bacterial diversity decreased in these finally enriched consortia compared with the original microbiota. Moreover, most ARGs quantified during the acclimation process became less abundant in the finally enriched microbial consortia. Microbial compositions of the two consortia as revealed by 16 S rRNA sequencing were similar to some extent, and the dominant genera Pseudomonas , Sphingobacterium, and Achromobacter were identified as the potential TC degraders. In addition, consortia SL and SI were capable of biodegrading TC (initial 50 mg/L) by 82.92% and 86.83% within 7 days, respectively. They could retain high degradation capabilities under a wide pH range (4−10) and at moderate/high temperatures (25–40 °C). Peptone with concentrations of 4–10 g/L could serve as a desirable primary growth substrate for consortia to remove TC through co-metabolism. A total of 16 possible intermediates including a novel biodegradation product TP245 were detected during TC degradation . Peroxidase genes, tet X-like genes and the enriched genes related to aromatic compound degradation as revealed by metagenomic sequencing were likely responsible for TC biodegradation.
研究领域:
环境微生物学
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生物修复
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分子生态学
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宏基因组学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2019
·
IF 4.527
Sicheng Shao,Yongyou Hu,Jianhua Cheng,Yuancai Chen
In this study, the characteristics of biodegradation of oxytetracycline (OTC) by strain Ochrobactrum sp. KSS10 were studied under various environmental conditions, including initial OTC concentrations, variable temperature, initial pH, and diverse carbon sources. The capability of this bacterial strain for performing simultaneous OTC degradation and nitrate reduction was also explored under aerobic conditions . An OTC degradation ratio of 63.33% and a nitrate removal ratio of 98.64% were obtained within 96 h. In addition, removal of OTC and ammonia from synthetic aquaculture wastewater by a Moving Bed Biofilm Reactor (MBBR) and changes in the resistant genes of microbial communities were also investigated. The results demonstrated that the strain KSS10 was the dominant contributor in OTC and ammonia removal in the MBBR chamber. It removed almost all ammonia and approximately 76.42% of OTC. The abundances of genes tet L, tet X and intI 1 were reduced by the MBBR, but the abundance of tet G and tet M were increased due to horizontal and vertical gene transfers. Such a result can potentially be used by the strain KSS10 for removing antibiotics and nitrogen from aquaculture wastewater during pre-treatment.
研究领域:
环境工程
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微生物学
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废水处理
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水产养殖
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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
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DOI
PubMed
高影响因子
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