BIOTECHNOLOGY AND BIOPROCESS ENGINEERING
·
2015
·Vol. 19
·期 6
·965-972
·
IF 1.113
Li Naiqiang,Chou Howard,Yu Lijun,Xu Yan
Cadaverine, as a biogenic amine, is an important platform chemical for the production of industrial polymers, such as polyamides, polyurethanes, and nylon. Previous efforts focused on the bio-based production of cadaverine using two lysine decarboxylases of Escherichia coli CadA and LdcC. In this study, we report the biotransformation of cadaverine using a lysine decarboxylase from Klebsiella oxytoca . Codon optimization of the gene encoding this enzyme was carried on for the heterologous expression in E. coli , which led to a system that converted more than 24% lysine-HCl to cadaverine compared to the same system expressing CadA. The system was further optimized by using three different inducible promoters to control the expression of lysine decarboxylase gene of K. oxytoca in E. coli . The final optimized system converted lysine-HCl to cadaverine at a conversion rate of 0.133%/min/g. When the optimized system described above is coupled to an industrial process, the combined process has the potential to produce cadaverine with high conversion efficiency (46%) from sugar.
研究领域:
生物化学
·
合成生物学
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工业微生物学
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DOI
高影响因子
PLoS Pathogens
·
2025
·Vol. 21
·期 1
·e1012787
·
IF 4.9
Tingting Wang,Huaizhi Yang,Qiushuang Sheng,Ying Ding,Jian Zhang,Feng Chen,Jianfeng Wang,Lei Song,Xuming Deng
Hypervirulent Klebsiella pneumoniae (hvKP) poses an alarming threat in clinical settings and global public health owing to its high pathogenicity, epidemic success and rapid development of drug resistance, especially the emergence of carbapenem-resistant lineages (CR-hvKP). With the decline of the “last resort” antibiotic class and the decreasing efficacy of first-line antibiotics, innovative alternative therapeutics are urgently needed. Capsule, an essential virulence determinant, is a major cause of the enhanced pathogenicity of hvKP and represents an attractive drug target to prevent the devastating clinical outcomes caused by hvKP infection. Here, we identified isoferulic acid (IFA), a natural phenolic acid compound widely present in traditional herbal medicines, as a potent broad-spectrum K . pneumoniae capsule inhibitor that suppresses capsule polysaccharide synthesis by increasing the energy status of bacteria. In this way, IFA remarkably reduced capsule thickness and impaired hypercapsule-associated hypermucoviscosity phenotype (HMV), thereby significantly sensitizing hvKP to complement-mediated bacterial killing and accelerating host cell adhesion and phagocytosis. Consequently, IFA facilitated effective bacterial clearance and thus remarkably protected mice from lethal hvKP infection, as evidenced by limited bacterial dissemination and a significant improvement in survival rate. In conclusion, this work promotes the development of a capsule-targeted alternative therapeutic strategy for the use of the promising candidate IFA as an intervention to curb hvKP infection, particularly drug-resistant cases.
Hypervirulent Klebsiella pneumoniae (hvKP) is becoming an imminent threat to public health because of the constant emergence of drug resistance and its devastating clinical outcomes. Meanwhile, the both notorious phenotypes are integrated to create carbapenem-resistant and hypervirulent K . pneumoniae (CR-hvKP), which leads to a scarcity of effective treatments. Therefore, there is an increasing urgent need for new therapeutics other than antibiotics. The indispensable role of capsule in immune evasion and pathogenesis renders it a promising target for developing novel alternative strategies to combat hvKP infections. In this study, we identified the small natural compound isoferulic acid (IFA) as a potent broad-spectrum inhibitor of K . pneumoniae capsule. Hypercapsule-associated hypermucoviscosity (HMV), a characteristic phenotype that has been shown to play a distinct and critical role in the pathogenesis of hvKP, is significantly impaired by IFA. RNA-seq analysis revealed that IFA interferes with the biosynthesis of capsule polysaccharide through altering bacterial metabolism status. Consequently, IFA sensitizes hvKP to serum killing and impedes capsule- and HMV-mediated resistance to adherence and phagocytosis. In vivo, IFA treatment facilitates effective host clearance and thereby systemically protects mice against hvKP infection. Our research sheds light on the development of capsule-targeted drug and provides an effective lead compound that may contribute to the management of hvKP infections as an intervention.
研究领域:
微生物学
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传染病学
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药物开发
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产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2014
·Vol. 99
·期 5
·2431-2439
·
IF 3.811
Yu Lei,Zhang Xiao-yu,Xie Tian,Hu Jin-mei,Wang Shi,Li Wen-wei
Reduction of azo dye methyl red coupled with aerobic respiration by growing cultures of Klebsiella oxytoca GS-4-08 was investigated. In liquid media containing dye and 0.6 % glucose in a mineral salts base, 100 mg l −1 of the dye are completely removed in 3 h under shaking conditions. The dye cannot be aerobically decolorized by strain GS-4-08 without extra carbon sources, indicating a co-metabolism process. Higher initial dye concentration prolonged the lag phase of the cell growth, but final cell concentrations of each batches reached a same level with range from 6.3 to 7.6 mg l −1 after the dye adaption period. This strain showed stronger dye tolerance and decolorization ability than many reported strains. Furthermore, a new intracellular oxygen-insensitive azoreductase was isolated from this strain, and the specific activity of enzyme was 0.846 and 0.633 U mg −1 protein in the presence of NADH and NADPH, respectively. N , N dimethyl- p -phenylenediamine and anthranilic acid were stoichiometrically released from MR dye, indicating the breakage of azo bonds accounts for the intracellular decolorization. Combining the characteristics of azoreductase, the stoichiometry of EMP, and TCA cycle, the electron transfer chain theory of aerobic respiration, and the possible mechanism of aerobic respiration coupled with azo reduction by K. oxytoca GS-4-08 are proposed. This study is expected to provide a sound theoretical basis for the development of the K. oxytoca strain in aerobic process for azo dye containing wastewaters.
研究领域:
微生物学
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环境科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2025
·
IF 6.6
Wenjie Yu,Yifan Zhang,Jinwang Li,Junru Li,Keju Li,Fangjian Ning,Xiali Guo,Xueyong Huang,Liping Luo
Scrophularia ningpoensis honey (SNH) is a type of honey derived from a traditional Chinese medicinal plant, with considerable potential value. Klebsiella pneumoniae , one of the most threatening pathogens worldwide, is also among the leading causative agents of wound infections, postoperative complications, and trauma-related skin and soft tissue infections. However, research on SNH remains limited, particularly regarding its compound composition and its ability to combat K. pneumoniae . In this study, the physicochemical properties of SNH were comprehensively characterised, revealing its high quality. SNH also demonstrated superior antibacterial activity compared to seven other types of honey. Furthermore, pathways such as valine, leucine, and isoleucine biosynthesis, as well as pantothenate and CoA biosynthesis, have been found to contribute to the antibacterial activity of SNH. To identify the active constituents, SNH was sequentially extracted with solvents of varying polarities and analyzed by UPLC-MS/MS, resulting in the identification of 157 metabolites. Among them, chlorogenic acid and chrysin were identified as potential key compounds responsible for the antibacterial effects against K. pneumoniae . This study systematically elucidated, for the first time, the physicochemical characteristics and chemical composition of SNH and demonstrated its strong antibacterial properties, providing an experimental basis for its further development and application.
研究领域:
微生物学
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药理学
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植物学
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生物化学
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产品关联
DOI
高影响因子
Scientific Reports
·
2016
·Vol. 6
·期 1
·1-11
·
IF 5.228
Yu Lei,Tang Qing-wen,Zhang Yu-jia,Chen Rong-ping,Liu Xin,Qiao Wei-chuan,Li Wen-wei,Ruan Hong-hua,Song Xin
In this work, the effect of cultivation factors on the flocculation efficiency (FE) of bioflocculant P-GS408 from Klebsiella oxytoca was optimized by the response surface methodology. The most significant factor, i.e . culture time, was determined by gray relational analysis. A total of 240 mg of purified P-GS408 was prepared from 1 liter of culture solution under the optimal conditions. GC-MS analysis results indicated that the polysaccharide of P-GS408 mainly contains Rhamnose and Galactose, and the existence of abundant hydroxyl, carboxyl and amino groups was evidenced by FTIR and XPS analyses. With the aid of Fe 3+ , the FE of kaolin solution by P-GS408 could achieve 99.48% in ten minutes. Functional groups of polysaccharide were involved in the first adsorption step and the zeta potential of kaolin solution changed from −39.0 mV to 43.4 mV in the presence of Fe 3+ and P-GS408. Three-dimensional excitation-emission (EEM) fluorescence spectra demonstrates that the trivalent Fe 3+ and Al 3+ can bind efficiently with P-GS408, while those univalent and divalent cations cannot. With the help of SEM images, FTIR, zeta potential and EEM spectra, we proposed the P-GS408 flocculation mechanism, which consists of coordination bond combination, charge neutrality, adsorption and bridging, and net catching.
研究领域:
微生物学
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环境科学
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DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Wen-Ba Wang,Jia-Yang Wan,Dao-Jun Yu,Hai-Xia Du,Hui-Fen Zhou,Hai-Tong Wan,Jie-Hong Yang
Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKp) infection poses a significant global public health challenge, with the misuse of antibiotics further contributing to the development of resistance and triggering harmful inflammatory responses. Outer membrane vesicles (OMVs) released by CRKp under sub-lethal concentration of MEM pressure (KOMV-MEM) exhibit enhanced virulence and greater efficiency in transferring resistance genes.Methods: We investigated the inhibitory effects of chlorogenic acid (CA) on KOMV-MEM characteristics and its protective role in KOMV-MEM infected mice. Based on LC-MS proteomic analysis of vesicles, we screened for potential targets of KOMV-MEM in promoting macrophage (MØ) pyroptosis pathways and inducing resistance gene transfer. Subsequently, computational predictions and experimental validation were performed to determine how CA regulates these mechanisms.Results: This study confirmed that, under MEM pressure, the exacerbated infection levels in CRKp-inoculated mice are attributable to the high virulence of KOMV-MEM. Computational and experimental results demonstrated that CA inhibits pyroptosis by reducing MØ capture of KOMV-MEM through blocking the interaction between GroEL and LOX-1. Furthermore, CA prevents the spread of resistance genes by disrupting the conjugation and transfer processes between KOMV-MEM and recipient bacteria. Finally, in vitro and in vivo assays showed that CA inhibits KOMV-MEM resistance enzymes, thereby preventing the hydrolysis of MEM in the environment and depriving susceptible bacteria of protection.Discussion: These findings provide the first confirmation that CA can inhibit both the virulence and the transmission of drug resistance in KOMV-MEM. This underscores the potential of CA treatment as a promising antimicrobial strategy against CRKp infection.
研究领域:
微生物学
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药理学
·
感染与免疫
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产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2017
·Vol. 83
·期 10
·
IF 3.807
Lei Yu,Ming-yue Cao,Peng-tao Wang,Shi Wang,Ying-rong Yue,Wen-duo Yuan,Wei-chuan Qiao,Fei Wang,Xin Song
Biohydrogen production from the pulp and paper effluent containing rich lignocellulosic material could be achieved by the fermentation process. Xylose, an important hemicellulose hydrolysis product, is used less efficiently as a substrate for biohydrogen production. Moreover, azo dyes are usually added to fabricate anticounterfeiting paper, which further increases the complexity of wastewater. This study reports that xylose could serve as the sole carbon source for a pure culture of Klebsiella oxytoca GS-4-08 to achieve simultaneous decolorization and biohydrogen production. With 2 g liter−1 of xylose as the substrate, a maximum xylose utilization rate (URxyl) and a hydrogen molar yield (HMY) of 93.99% and 0.259 mol of H2 mol of xylose−1, respectively, were obtained. Biohydrogen kinetics and electron equivalent (e− equiv) balance calculations indicated that methyl red (MR) penetrates and intracellularly inhibits both the pentose phosphate pathway and pyruvate fermentation pathway, while methyl orange (MO) acted independently of the glycolysis and biohydrogen pathway. The data demonstrate that biohydrogen pathways in the presence of azo dyes with sulfonate and carboxyl groups were different, but the azo dyes could be completely reduced during the biohydrogen production period in the presence of MO or MR. The feasibility of hydrogen production from industrial pulp and paper effluent by the strain if the xylose is sufficient was also proved and was not affected by toxic substances which usually exist in such wastewater, except for chlorophenol. This study offers a promising energy-recycling strategy for treating pulp and paper wastewaters, especially for those containing azo dyes.IMPORTANCE The pulp and paper industry is a major industry in many developing countries, and the global market of pulp and paper wastewater treatment is expected to increase by 60% between 2012 and 2020. Such wastewater contains large amounts of refractory contaminants, such as lignin, whose reclamation is considered economically crucial and environmentally friendly. Furthermore, azo dyes are usually added in order to fabricate anticounterfeiting paper, which further increases the complexity of the pulp and paper wastewater. This work may offer a better understanding of biohydrogen production from xylose in the presence of azo dyes and provide a promising energy-recycling method for treating pulp and paper wastewater, especially for those containing azo dyes.
研究领域:
环境科学
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微生物学
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产品关联
DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
·
2012
·
IF 4.98
Xiaoyan Wang,Zuoming Zhou,Guohua Jing
Magnetic poly(styrene–glycidyl methacrylate) porous microspheres (MPPM) with high magnetic contents were prepared by surfactant reverse micelles and emulsion polymerization of monomers, in which the well-dispersed Fe 3 O 4 nanoparticles were modified by polyethylene glycol (PEG) and oleic acid (OA) respectively. The characterizations showed that both of the OA–MPPM and the PEG–MPPM were ferromagnetic, however, the OA–MPPM was used to immobilize the bacteria for more advantages. Therefore, the effects of monomer ratio, surfactant, crosslinker and amount of Fe 3 O 4 on the structure, morphology and magnetic contents of the OA–MPPM were investigated. Then, the OA–MPPM was utilized to immobilize Klebsiella sp. FD-3, an iron-reducing bacterium for Fe(III)EDTA reduction applied in NO x removal. Compared with free bacteria, the immobilized FD-3 showed a better tolerance to the unbeneficial pH and temperature conditions.
研究领域:
环境科学
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微生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2018
·
IF 6.434
Hong-cheng Fan,Jing Yu,Rong-ping Chen,Lei Yu
A novel bioflocculant, A-GS408, produced by Klebsiella oxytoca GS-4-08 cultured in acetonitrile (ACN) as sole nitrogen source was investigated in this study. A complete degradation of 1 g l −1 of ACN was achieved in 350 h, and 4.6 g of crude A-GS408 can be obtained in one litter of synthetic medium. The as-prepared bioflocculant exhibits good flocculation efficiency (over 90%) toward Kaolin solution with the aid of Fe 3+ . Chemical analysis showed that the bioflocculant was mainly composed of polysaccharides (46.3%) and proteins (20.6%). FTIR and XPS results indicated the abundant carboxyl, amine and hydroxyl groups in A-GS408 s, which play an important role on Pd 2+ and Cu 2+ adsorption. The adsorption of heavy metals can be well stimulated by Freundlich isotherm equation, and the K f was up to 439.2 mg 1-1/n l 1/n g −1 and 112.2 mg 1-1/n l 1/n g −1 for Pb 2+ and Cu 2+ , respectively. The kinetic fitting results proved that the adsorption of heavy metals by A-GS408 was chemisorption. This study may provide a new method for preparation of bioflocculant, which can not only degrade toxic compound i . e ., acetonitrile, but also can reuse considerable nitrogen source from nitrile-containing wastewater.
研究领域:
环境生物学
·
微生物学
✓ 已验证
DOI
高影响因子
PHYSIOLOGICAL AND MOLECULAR PLANT PATHOLOGY
·
2024
·
IF 2.8
Zhe Han,Shengyi Wang,Ao Gao,Meiqi Dong,Yufeng Xiao,Hongyu Pan,Lining Zheng,Hao Zhang
Tomato wilt disease, caused by Fusarium oxysporum f. sp. lycopersici , is a major soil-borne disease affecting tomato cultivation. In this study, two strains exhibiting significant control effects on F. oxysporum f. sp. lycopersici and tomato growth-promoting effects were isolated from the rhizosphere. Through physiological and biochemical identification, as well as 16S rRNA identification, these strains were identified as Enterobacter quasihormaechei L33 and Klebsiella oxytoca TL2, respectively. And the two strains of bacteria were confirmed to have no antagonistic effect through antagonistic compatibility tests. Notably, when these strains were mixed in a ratio of 5:1, they demonstrated remarkable antifungal activity. The mixed strains induced mycelium swelling, necrosis, and rupture in F. oxysporum f. sp. lycopersici , resulting in a 56.65 % inhibition of mycelial fresh weight. Additionally, they inhibited spore production with an inhibition rate of 787.5 %, and the inhibition rate of the lipopeptide produced reached 93.80 % at 50 mg/mL. Furthermore, in potting experiments, the mixed strains reduced the disease incidence by 36.25 % after 8 weeks. Additionally, compared to the control group, the mixed bacterial strain group enhanced fresh weight, plant height, chlorophyll a and b levels, and root activities by 96.31 %, 18.51 %, 184.48 %, 53.03 %, and 44.31 %, respectively. In addition, mixed strains can inhibit the cell wall degrading enzymes produced by Fusarium oxysporum f sp., induce plant defense enzymes, including increased activity of peroxidase, catalase, and superoxide dismutase, and reduce the decrease in malondialdehyde levels. The mixed strains could colonize tomato plant roots. Overall, these findings suggest a potential biocontrol agent deriving from the mixed strains against tomato wilt disease.
研究领域:
植物病理学
·
微生物学
✓ 已验证
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Maruthupandy Muthuchamy,Rajivgandhi Govindan,Kadaikunnan Shine,Veeramani Thangasamy,Naiyf S. Alharbi,Muneeswaran Thillaichidambaram,Jamal M. Khaled,Jun-Li Wen,Khalid F. Alanzi
In this study graphene/chitosan nanoparticles (GR/CS NCs) were developed. The homogenous combination of GR and CS was confirmed by FTIR spectroscopy. The combination of CS with GR sheets reduced the XRD intensity of the GR peak in GR/CS NCs, while TEM images revealed the immobile CS coating of GR sheets. Further, the anti-biofilm activity of GR/CS NCs was tested. The tests showed that the formation of biofilm by Pseudomonas aeruginosa and Klebsiella pneumoniae was inhibited at 40□g/mL GR/CS NCs up to 94 and 92 %, respectively. The intracellular and cell surface damage of the bacteria was observed by CLSM and SEM. Also, GR/CS NCs produced a toxic effect of 90 % on Artemia franciscana at 70□g/mL upon 24 h incubation. The recorded properties of the synthesized GR/CS NCs qualify them as potential agents against multi-drug resistant bacteria.
研究领域:
微生物学
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纳米医学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG RESISTANCE UPDATES
·
2026
·
IF 22
Liang Wang,Jie Zhu,Jingnan Lv,Yunmiao Xu,Jiayao Lin,Yan Qian,Qizhao Gao,Yicheng Wen,Yaxuan Zhai,Zhichen Zhu,Haifang Zhang,Liang Chen,Hong Du
Aims The worldwide spread of carbapenem-resistant Klebsiella pneumoniae (CRKP) has posted a global threat. Treatment options for CRKP are limited, especially for strains producing New Delhi metallo-β-lactamase (NDM). The emergence of the siderophore antibiotic cefiderocol has brought hope; however, recent clinical and research data show that NDM-producing K. pneumoniae have a high rate of resistance to cefiderocol, and the reason remains unclear. Methods This study focused on the dynamic changes in K.pneumoniae under host nutritional immunity and cefiderocol stress. It identified one of the main reasons for the strong cefiderocol resistance in NDM-producing strains. Further studies found that the JNMCOFLA_01041 gene plays an important role in this process and is crucial for cefiderocol resistance and virulence in K.pneumoniae . Results Under host nutritional immunity and cefiderocol stress, K.pneumoniae is exposed to increasing oxidative stress. This oxidative stress results in a dynamic pattern of rapid increases in intracellular Zn²⁺ concentrations. This autonomous changes in Zn²⁺ levels in response to cefiderocol challenge can rapidly increase NDM enzyme activity and enhance the MIC, which may be one of the main reasons for the high cefiderocol minimal inhibit concentration (MIC) in NDM-producing strains. Further study identified a key gene, JNMCOFLA_01041 , for Zn²⁺ and hemin absorption in K. pneumoniae . The Zn²⁺ acquisition function plays an important role in oxidative stress resistance, NDM activity, metabolism, and even pathogenicity. Conclusions Taken together, our research highlights the impact of dynamic changes in bacterial metal ion concentrations on bacterial survival and drug resistance under complex host conditions. It emphasizes that, while using antimicrobial drugs, monitoring and regulating changes in the bacterial internal environment under pathological conditions is crucial for maximizing anti-infective efficacy. Furthermore, JNMCOFLA_01041 could be a target of novel drug and vaccine development.
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）