BIOMEDICINE & PHARMACOTHERAPY
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2023
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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
Foods
·
2022
·Vol. 11
·期 17
·2660
·
IF 5.561
Xiayu Liu,Xinxin Pang,Yansha Wu,Yajing Wu,Ying Shi,Xinglin Zhang,Qihe Chen
Mannosylerythritol lipids-A (MEL-A) is a novel biosurfactant with multiple biological effects. The synergistic antibacterial activity and mechanism of MEL-A and lactic acid (LA) againstListeria monocytogeneswere investigated. The synergistic effect resulted in a significant increase in the antibacterial rate compared to LA treatment alone. Genome-wide transcriptomic analysis was applied to deeply investigate the synergistic antibacterial mechanism. Gene Ontology (GO) enrichment analysis showed that the synergy between MEL-A and LA affected many potential cellular responses, including the sugar phosphotransferase system, carbohydrate transport, and ribosomes. KEGG enrichment analysis showed that the PTS system and ribosome-related pathways were significantly enriched. In addition, synergistic treatment affected locomotion and membrane-related cellular responses in GO enrichment analysis and carbohydrate metabolism and amino acid metabolism pathways in KEGG enrichment analysis compared to LA treatment alone. The accuracy of the transcriptome analysis results was verified by qPCR (R2= 0.9903). This study will provide new insights for the prevention and control ofL. monocytogenes.Keywords:Mannosylerythritol lipids-A (MEL-A);lactic acid;Listeria monocytogenes;RNA-Seq
研究领域:
微生物学
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分子生物学
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食品安全
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基因组学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-14
·
IF 15.7
He Wenyan,Huan Xueting,Li Yinchuan,Deng Qisen,Chen Tao,Xiao Wen,Chen Yijun,Ma Lingman,Liu Nan,Shang Zhuo,Wang Zongqiang
The rapid emergence of difficult-to-treat multidrug-resistant pathogens, combined with the scarcity of antibiotics possessing novel mechanisms, poses a significant threat to global public health. Here, we integrate the synthetic-bioinformatic natural product approach with peptide optimization to unveil the antibiotic-producing potential of Paenibacillaceae bacteria. Our culture-independent approach led to the discovery of paenimicin, a novel 11-mer depsi -lipopeptide featuring an unprecedented dual-binding mechanism. By sequestering the phosphate and hydroxyl groups of lipid A in Gram-negative bacteria, as well as the phosphate groups of teichoic acids in Gram-positive bacteria, paenimicin exhibits potent and broad-spectrum efficacy against MDR pathogens in vitro and in vivo models. Paenimicin demonstrates no detectable resistance, favorable pharmacokinetics and low nephrotoxicity, positioning it as a promising candidate for treating severe and urgent MDR infections.
研究领域:
抗菌研究
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生物信息学
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微生物学
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药理学
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传染病学
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合成生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Chen Liu,Jing-ying Xu,Jun-feng Qi,Yan-jie Liu,Jia-wei Kang,Heng-yu Wang,Si-yi Chen,Zheng Huang,Bin Lu
Endotoxin in water affects water quality and human health. Detecting endotoxin in water required sensitive, accurate and stable methods due to the large amounts of interferences and highly varied endotoxin levels in different water. For the first time, a novel nanobiocomposite sandwich immunosensor was fabricated for accurate and convenient endotoxin determination by using molecularly imprinted nano-membrane (MIM) and nature antibody selective to different epitopes of endotoxin as affinity molecules simultaneously. Endotoxin-imprinted MIM was prepared on the surface of microplate by dopamine self-polymerization method. MIM enriched endotoxin by binding polysaccharides selectively. Then primary antibody specific to lipid A of endotoxin quantified the endotoxin captured by MIM. Using the high stability of MIM to harsh conditions and the high accuracy of nature antibody as affinity molecules simultaneously, selective sample pre-treatment was designed into immunosensor effectively. The achieved immunosensor detected endotoxin in different diluted or un-diluted water sensitively and accurately. The LOD, LOQ and linearity of the immunosensor were 4 × 10 −6 μg/L, 1.3 × 10 -5 μg/L and 10 -5 -10 5 μg/L respectively. While only proper diluted water samples could be accurately detected by limulus amebocyte lysate assays (LAL). The immunosensor also had much higher sensitivity and accuracy than indirect competitive ELISA which used the same primary antibody. By combing sample pre-treatment with immunosensor, the nanobiocomposite sandwich immunosensor provides a solution to detect endotoxin in water accurately and conveniently.
研究领域:
环境科学
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分析化学
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纳米技术
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生物技术
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）