Scientific Reports
·
2019
·Vol. 9
·期 1
·1-9
·
IF 4.011
Shao Yongni,Gu Weimin,Jiang Linjun,Zhu Yiming,Gong Aiping
As an ideal raw material for the production of astaxanthin, H . pluvialis was drawing attention during the last few years, there are some research topics initiated to find out the synthetic pathway of astaxanthin in H . pluvialis . In this study, confocal microscopic Raman technology was utilized to analyze the point-by-point mapping for H . pluvialis , and the visualization of pigment such as carotenoid and astaxanthin content were achieved. By comparing the Raman spectra of H . pluvialis and standard product of astaxanthin, and using the C = C stretching vibration of the Raman intensity as the main indicator for carotenoids, the visual spatial distribution for the carotenoids content was obtained. The MCR-ALS was applied to analyze the Raman data of H . pluvialis , and the information of astaxanthin was extracted to achieve real-time spatial distribution. The visualization of astaxanthin content shows that MCR-ALS is very effective for extracting the information of astaxanthin content from H . pluvialis . By exploring the spatial distribution of carotenoids and astaxanthin contents, analyzing the spatial distribution rules during its growth, Raman spectroscopy technology can be utilized to investigate the internal components of the pigment (ataxanthin, etc.) in H . pluvialis , which make it as an effective methodology to monitor the accumulation and changing mechanism of pigment content in microalgae.
研究领域:
生物化学
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光谱学
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藻类研究
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高影响因子
Advanced Science
·
2023
·
IF 15.1
Jinju Cai,Jingru Shi,Chen Chen,Mengping He,Zhiqiang Wang,Yuan Liu
The emergence and prevalence of mobile colistin resistance gene mcr have dramatically compromised the clinical efficacy of colistin, a cyclopeptide antibiotic considered to be the last option for treating different-to-treat infections. The combination strategy provides a productive and cost-effective strategy to expand the lifespan of existing antibiotics. Structural-activity relationship analysis of polymyxins indicates that the fatty acyl chain plays an indispensable role in their antibacterial activity. Herein, it is revealed that three saturated fatty acids (SFAs), especially sodium caprate (SC), substantially potentiate the antibacterial activity of colistin against mcr- positive bacteria. The combination of SFAs and colistin effectively inhibits biofilm formation and eliminates matured biofilms, and is capable of preventing the emergence and spread of mobile colistin resistance. Mechanistically, the addition of SFAs reduces lipopolysaccharide (LPS) modification by simultaneously promoting LPS biosynthesis and inhibiting the activity of MCR enzyme, enhance bacterial membrane damage, and impair the proton motive force-dependent efflux pump, thereby boosting the action of colistin. In three animal models of infection by mcr -positive pathogens, SC combined with colistin exhibit an excellent therapeutic effect. These findings indicate the therapeutic potential of SFAs as novel antibiotic adjuvants for the treatment of infections caused by multidrug-resistant bacteria in combination with colistin.
研究领域:
药理学
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微生物学
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传染病学
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分子生物学
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高影响因子
Frontiers in Cellular and Infection Microbiology
·
2026
·
IF 5.5
Yujuan Li,Yi Yang,Ting Zhou,Jing Zhou,Jie Hu,Shuangshuang Liang,Zhenhua Xie,Qing Cheng,Yachao Jiang,Chao Jiang,Qing Liu
Amid the growing antibiotic resistance crisis, colistin remains a last-line therapeutic option for multidrug-resistant (MDR) Gram-negative bacterial infections. However, the emergence and rapid dissemination of plasmid-mediated colistin resistance gene (mcr) have markedly reduced its clinical effectiveness. Utilizing colistin adjuvants to restore its antibacterial potency is a promising strategy to combat this threat. In this study, we aimed to investigate the synergistic effects of α-terpineol in combination with colistin against colistin-resistant MDR Escherichia coli (E. coli) and to elucidate the underlying mechanisms of this synergy. In vitro synergistic activity was evaluated using checkerboard microdilution assays, time-kill curve analyses, and resistance development studies. Mechanistic insights were obtained through transcriptomic analysis and fluorescence-probe based assays. In vivo efficacy was validated using Galleria mellonella and mouse acute peritonitis infection models. The results showed that the combination of α-terpineol and colistin exhibited synergistic bactericidal activity and suppressed the development of colistin resistance. α-Terpineol increased inner- and outer-membrane fluidity in E. coli, thereby enhancing colistin uptake. Furthermore, it inhibited superoxide dismutase (SOD) activity, preventing the conversion of O2·– to H2O2 and causing superoxide accumulation. Elevated O2·– levels damaged iron–sulfur clusters and impaired respiratory function. Together with the proton motive force (PMF) dissipation, these effects severely impaired ATP synthesis, ultimately sensitizing MDR E. coli to colistin. The combination also showed significant therapeutic efficacy in animal models. Our findings identify α-terpineol as a promising colistin adjuvant that restores antibacterial activity by disrupting membrane integrity and impairing antioxidant defenses, offering a viable strategy for treating MDR Gram-negative bacterial infections.
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Antibiotics-Basel
·
2025
·Vol. 15
·期 1
·
IF 4.6
Yongqing Liu,Huangwei Song,Muchen Zhang,Junyao Jiang,Yan Zhang,Jian Xu,Xi Xia,Shangshang Qin,Jianzhong Shen,Yang Wang
Background:The reintroduction of colistin has led to the rapid emergence of colistin-resistant strains, significantly diminishing its therapeutic efficacy. This presents a need for effective adjuvants to restore colistin efficacy.Approach: We screened the colistin adjuvants through a high-throughput method and then evaluated their synergistic effects and underlying mechanisms.Results: We identified β,β-dimethylacrylalkannin (β,β-Dim), a naphthoquinone compound derived from Lithospermum erythrorhizon, as a potent colistin adjuvant (fractional inhibitory concentration index (FICI) < 0.5). β,β-Dim enhanced colistin activity against 4 of 6 susceptible strains and all 18 colistin-resistant strains carrying either plasmid-bornemcrgenes (mcr-1,mcr-3,mcr-8, andmcr-9) or chromosomal two-component system (TCS) mutations (pmrA/B,phoP, andmgrB). These strains includedKlebsiella pneumoniae,Escherichia coli,SalmonellaTyphimurium,Pseudomonas aeruginosa, andAcinetobacter baumannii. The combination reduced the minimum inhibitory concentrations (MICs) of colistin by 4–1024-fold (from 512 to ≤2 µg/mL). Mechanistically, colistin-mediated outer membrane permeabilization facilitates β,β-Dim entry. Once internalized, β,β-Dim interacts with cytoplasmic membrane phospholipids and disrupts membrane biofunction. Further analysis showed that LPS transport and efflux pump activity were impaired, leading to LPS accumulation in the cytoplasmic membrane and increased intracellular colistin content. These processes elevated reactive oxygen species (ROS) production and markedly reduced ATP levels. In a murine infection model, β,β-Dim (2 mg/kg) combined with colistin (0.2 mg/kg) markedly increased survival from 20% (colistin alone) to 80%.Conclusions:These findings highlight that β,β-Dim combined with colistin is a promising therapeutic strategy for infections caused by colistin-resistant pathogens.
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CURRENT MICROBIOLOGY
·
2026
·Vol. 83
·期 8
·424
·
IF 2.8
Xu Jialin,Yan Bohu,Fu Qifu,Li Haoyu,Jiang Zonghan,Zhou Rushun,Chen Xiaojun,Sun Zhiliang,Wang Yanan,Li Jiyun
In response to the critical challenge of colistin resistance in animal production, we examined the occurrence and genetic features of mcr-1 -positive E. coli isolates collected from livestock in Hunan province, China, between 2016 and 2021. A total of 1,358 animal samples from chickens and pigs were collected and screened. Monitoring data indicates that nineteen mcr-1 -positive E. coli isolates (1.40%) were identified, and all were resistant to colistin and tetracycline. The prevalence rate of mcr-1 positive E. coli has significantly declined since 2017 and has remained consistently low. Most isolates (89.47%) exhibited multidrug resistance and carried multiple antibiotic resistance genes, including tet (A) , sul3, bla TEM-1B, while a subset of strains (21.05%) harbored quinolone resistance-associated point mutations in gyrA , parC , and parE . Multi-locus sequence typing identified 14 sequence types, with ST48 being the most frequent (21.05%), and five clonal complexes, with CC10 as the predominant lineage (52.63%). Plasmid analysis revealed that 68.42% of the isolates carried plasmids, predominantly IncX4 (36.84%), and 57.89% of isolates harbored conjugative plasmids with complete relaxase and MPF system components. The mcr-1 gene was found within three main genetic arrangements: (i) mcr-1-pap2, (ii)IS Apl1-mcr-1-pap2, and (iii) IS Apl1-mcr-1-pap2- IS Apl1 . These findings highlight the potential for dissemination of mcr-1 in animal-derived E. coli and underscore the importance of monitoring and controlling antimicrobial resistance in livestock.
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BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
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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JOURNAL OF CHROMATOGRAPHY A
·
2020
·
IF 4.049
Xiao-Hua Zhang,Qian Zhou,Zhi Liu,Xiang-Dong Qing,Jing-Jing Zheng,Shu-Ting Mu,Pan-Hua Liu
Retention time shifts in second-order calibration-assisted chromatographic analysis seriously impact the modeling and quantitative accuracies in complex systems. In this work, three second-order methods, i.e. alternating trilinear decomposition (ATLD) algorithm, multivariate curve resolution-alternating least squares (MCR-ALS), alternating trilinear decomposition-assisted multivariate curve resolution (ATLD-MCR), were compared their performance to process liquid chromatographic data in the presence of retention time shifts and overlapped peaks. Firstly, the validation samples contain five tea polyphenols at three concentrate levels within the calibration ranges, helped to understand, visualize and interpret these features of three second-order multivariate methods. Secondly, experimental data were studied concerning the determination of polyphenols in Chinese tea samples by HPLC-DAD. The results showed that all three second-order multivariate methods realized satisfactory quantification for five targeted analytes in Pu-Er ripe tea samples and Green tea samples even with the interference of slight retention time shifts, average recoveries were 91.23% –113.16% for ATLD, 89.96%–115.96% for ATLD-MCR, 90.64%–117.60% for MCR-ALS, respectively. However, ATLD was disappointing in the case of larger time shifts (approx. 4.00 s and 6.40 s) occurring for the quantitative analysis of Black tea and Clinacanthus nutans tea, the average recoveries were just 67.33–84.05%. Relatively, MCR-ALS and ATLD-MCR were more significantly excellent, satisfactory results still can be obtained, the average recoveries for MCR-ALS and ATLD-MCR were in the range of 86.04–117.60% and 89.96–115.96%, respectively.
研究领域:
分析化学
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色谱学
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食品科学
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植物化学
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FOOD CHEMISTRY
·
2019
·
IF 5.399
Shao Hua Lu,Sha Sha Li,Bo Yin,Jia Ying Mi,Hong Lin Zhai
Diverse interferences often affect the determination of pesticide residues in various kinds of food, and complex pretreatments are necessary. An effective approach for the simultaneous quantitative analysis of multi-target components in different substrates was proposed, and applied to the determination of ternary pesticides in cherry tomatoes and red grape samples. By means of HPLC-DAD, the spectra were obtained under isocratic elution. Utilizing the Tchebichef image moments, unified quantitative models were established for the three target components in the samples with two different substrates, respectively. The correlation coefficients of leave-one-out cross-validation ( R loo - c v 2 ) of the obtained models were more than 0.9975. The predictive correlation coefficients ( R p 2 ) were more than 0.9831. Compared with the N-PLS and MCR-ALS methods, the proposed approach is not only more accurate and reliable, but also can extract essential information and expected to be a potential tool to rapidly quantify multi-component in different substrates without complex pretreatments.
研究领域:
分析化学
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食品科学
·
化学计量学
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JOURNAL OF APPLIED POLYMER SCIENCE
·
2022
·Vol. 139
·期 22
·52263
·
IF 3.057
Jie Zhang,Zongwei Guo,Jinpeng Ma,Lingxiao Song,Guorui Yang,Yuhui Ao,Lei Shang,Ming Li
As an important thermosetting resin, epoxy resin (EP) is widely used in the field of composite materials. Long storage time, rapid curing and low viscosity of one-component EP is ideal for preparing composite materials by vacuum assisted resin transfer molding (VARTM). For this sake, we developed and synthesized a new imidazole thermal latent curing agent, 4,7-diimidazol-2,1,3-benzothiadiazole (BTD-MZ 2 ) with a yield of about 75%. The curing behavior, thermal stability and storage time of the prepared EP system was studied by differential scanning calorimeter (DSC), thermal gravimetric analyzer (TGA), modular compact rheometer (MCR), respectively. DSC results showed that EP/17.5 wt% BTD-MZ 2 had a good latent period at low temperature, and can rapidly cure EP when heated to 150°C. TGA results show that BTD-MZ 2 promoted the formation of carbon residue and the residual carbon rate of EP/17.5 wt% BTD-MZ 2 is as high as 37.9%. MCR results show that the storage time of EP/17.5 wt% BTD-MZ 2 at 60°C can reach 850 min. In addition, it could play a role of catalyst used as co-curing agents with aromatic amines for EP. DSC test showed that the addition of 5 wt% BTD-MZ 2 reduced the activation energy of EP/4,4′-diaminodiphenylmethane (DDM) and promoted the curing reaction.
研究领域:
材料科学
·
化学工程
·
高分子科学
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BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Linlin Ding,Rui He,Yongjia Hu,Jian Liu,Paizati Hamidi,Yerzati Nurman,Lei Xu,Jianfeng Wang,Xuming Deng,Aslebek Zekriya,Ying Chen,Qingjie Li
The global spread of multidrug-resistant (MDR) bacteria is devastating health systems and economies worldwide, and this critical trend has revitalized antibiotic adjuvant research. The extensive dissemination of plasmid- or chromosome-mediated resistance genes emphasizes the importance of reshaping colistin sensitivity. Here, we report the discovery that Melissa officinalis essential oil isolated from Traditional Chinese medicine, effectively potentiates the bactericidal activities of colistin against mobile colistin resistance (MCR-1) positive Escherichia coli ( E. coli ). Mechanistic analysis demonstrated that Melissa officinalis essential oil interacts with the MCR-1 protein to disrupt LPS modification, while concurrently inducing microbial iron homeostasis disruption and oxidative damage. To enhance its essential oil-mediated therapeutic potential in clinical management, Melissa officinalis essential oil-loaded nanostructured lipid carrier (MOEO-NLC) was designed with improved biocompatibility and solubility. Encouragingly, the combination of MOEO-NLC and colistin reduced bacterial burden reduction and inflammatory response suppression in a peritonitis-sepsis model. Collectively, this study advances antibacterial tactics and underscores the transformative potential of MOEO-NLC in paving the way for enduring countermeasures against antibiotic-resistant threats.
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JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
·
2023
·
IF 5.2
Sheng Qiushuang,Wang Nan,Zhou Yonglin,Deng Xuming,Hou Xiaoning,Wang Jianfeng,Qiu Jiazhang,Deng Yanhong
BackgroundAdjuvant addition of approved drugs or foodborne additives to colistin might be a cost-effective strategy to overcome the challenge of plasmid-mediated mobile colistin resistance gene emergence, which poses a threat in the clinic and in livestock caused by infections with Gram-negative bacteria, especially carbapenem-resistant Enterobacteriaceae.MethodsChequerboard assay was applied to screen the colistin adjuvants from natural compounds. The killing–time curve, combined disc test and membrane permeation assay were conducted to identify the synergy efficacy of thymol and colistin in vitro. Thin-layer chromatography (TLC), LC-MS and fluorescence spectra were used to indicate the interaction of thymol and MCR-1. The potential binding sites were then investigated by molecular simulation dynamics. Finally, a thymol nanoemulsion was prepared with high-pressure homogenization as the clinical dosage form.ResultsThymol presented an excellent synergistic effect in vitro with colistin against Salmonella enterica serovar Typhimurium and Escherichia coli bacteria. Thymol addition, forming a complex with MCR-1, might interfere with the efficacy of MCR-1. Moreover, thymol strengthened colistin activity associated with potentiating membrane damage, destroying the biofilm and enhancing reactive oxygen species-mediated oxidative damage. Thymol nanoemulsion combined with colistin remarkably prevented the intestinal damage caused by S. Typhimurium infection, resulting in a survival rate higher than 60%.ConclusionsThis study achieved a promising thymol oral formulation as colistin adjuvant to combat S. Typhimurium infection, which could be used to extend the lifespan of colistin in clinical veterinary medicine.
研究领域:
微生物学
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药学
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传染病学
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兽医学
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2022
·
IF 4.831
Han Fu,Maogang Li,Mengjun Guo,Hongsheng Tang,Tianlong Zhang,Hua Li
The precise and accurate synthesis mechanism of typical energetic materials (EMs) intermediate is extremely important for the optimization of synthesis technology of EMs. In this research, on-line Raman spectroscopy technique combined with multivariate curve resolution-alternating least squares(MCR-ALS) method was proposed and used to investigate the synthesis mechanism of EMs intermediate (3,5-diamino-1,2,4-triazole, DAT). Initially, on-line Raman spectroscopy was applied to collect the Raman spectral data of DAT synthesis process. Secondly, principal component analysis (PCA), coupled with singular value decomposition (SVD) were used to determine the number of component of the reaction system and the components was 5. Thirdly, MCR-ALS was used to extract the pure Raman spectra and concentration curves of each substance of DAT synthesis process. During the MCR-ALS operation, evolving factor analysis (EFA) was choose to acquire the initial concentration estimation for MCR-ALS. Several constraints were selected to apply to ALS optimization including non-negative, closure, equality and correlation constraint. And the correlation coefficient between the Raman spectra and the actual Raman spectra of the hydrazine hydrochloride, dicyandiamide and DAT was calculated, their correlation coefficient R 2 were 0.9522, 0.9446, 0.9908 respectively which showed a good data fit of MCR-ALS method. Finally, according to the results of MCR-ALS analysis, the structure of the synthetic intermediates was successfully deduced and the mechanism of DAT synthesis was proposed. Hence, a precise and comprehensive method for analyzing the DAT synthesis reaction mechanism is proposed, which is helpful to provide a new idea for the analysis of the synthesis reaction mechanism of energetic materials.
研究领域:
化学
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含能材料
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分析化学
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过程分析技术
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光谱学
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高影响因子
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