Frontiers in Bioengineering and Biotechnology
·
2023
·
IF 5.7
Gui Shumin,Li Xisheng,Feng Mingming,Liu Hui,Huang Liwenhui,Niu Xinqing
In recent years, the treatment of Acinetobacter baumannii infections has become a pressing clinical challenge due to its increasing incidence and its serious pathogenic risk. The research and development of new antibacterial agents for A. baumannii have attracted the attention of the scientific community. Therefore, we have constructed a new pH-responsive antibacterial nano-delivery system (Imi@ZIF-8) for the antibacterial treatment of A. baumannii. Due to its pH-sensitive characteristics, the nano-delivery system offers an improved release of the loaded imipenem antibiotic at the acidic infection site. Based on the high loading capacity and positive charge of the modified ZIF-8 nanoparticles, they are excellent carriers and are suitable for imipenem loading. The Imi@ZIF-8 nanosystem features synergistic antibacterial effects, combining ZIF-8 and imipenem to eliminate A. baumannii through different antibacterial mechanisms. When the loaded imipenem concentration reaches 20 µg/mL, Imi@ZIF-8 is highly effective against A. baumannii in vitro. Imi@ZIF-8 not only inhibits the biofilm formation of A. baumannii but also has a potent killing effect. Furthermore, in mice with celiac disease, the Imi@ZIF-8 nanosystem demonstrates excellent therapeutic efficacy against A. baumannii at imipenem concentrations of 10 mg/kg, and it can inhibit inflammatory reaction and local leukocyte infiltration. Due to its biocompatibility and biosafety, this nano-delivery system is a promising therapeutic strategy in the clinical treatment of A. baumannii infections, providing a new direction for the treatment of antibacterial infections.
研究领域:
药学
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纳米技术
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微生物学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Xiao-Yi Chen,Qian-Long Wang,Wei-Xue Huang,Long-Wei Li,Lan-Cong Liu,Yi Yang,You-Jiao Wu,Shan-Shan Song,Hao Ma,Hua Zhou,Pei Luo
Bacterial peritonitis is a severe disease that diagnosis remains challenging for clinicians. Measuring biomarkers might be a rapid diagnostic method. The objective of this study was to analyze and evaluate the dynamic changes in HIF-1α concentration in serum exosomes during bacterial peritonitis. The pre-clinical application value of serum exosomal HIF-1α was evaluated via imipenem and cilastatin sodium (ICS) intervention in the bacterial peritonitis model. The new colorimetric method to quantitate dynamic expression changes of HIF-1α in serum exosomes during bacterial peritonitis was established by our team via using the gold seed-coated with aptamer-functionalized Au @ Au core-shell peroxidase mimic. The typical inflammatory cytokines of bacterial peritonitis were also measured. Following intramuscular administration with ICS, In-Vivo Xtreme imaging system was used to visualize abdominal infection extent. Meanwhile, HIF-1α concentration in rat serum exosomes and pro-inflammatory factors levels in serum were detected. The serum typical inflammatory cytokines levels were elevated in GFP-labeled E.coli induced bacterial peritonitis. The serum exosomal HIF-1α levels clearly increased at 12 h, reached the peak during 24–48 h, and then gradually decreased at 72 h. Following intramuscular administration with ICS, the abdominal infection extent, HIF-1α concentration in serum exosomes, and the serum pro-inflammatory factors levels were reduced at 24 h in GFP-labeled E. coli induced bacterial peritonitis model. The serum exosomal HIF-1α can be used as a biomarker in the early stage of bacterial peritonitis, which might provide the basic research in the pre-clinical for further predicting and monitoring the pathological process of bacterial peritonitis.
研究领域:
医学诊断
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药理学
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传染病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BACTERIOLOGY
·
2022
·
IF 3.476
Greater Kayode Oyejobi,Dongyan Xiong,Mengjuan Shi,Xiaoxu Zhang,Hang Yang,Heng Xue,Faith Ogolla,Hongping Wei
With the increasing morbidity and mortality rates associated with multidrug-resistant bacteria, interest in bacteriophage therapy has been revived. However, bacterial resistance to phage infection threatens the usefulness of phage therapy, especially its inclusion in modern medicine. Multidrug-resistant Acinetobacter baumannii is a top-priority pathogen requiring urgent intervention and new therapeutic approaches, such as phage therapy. Here, we experimentally adapted A. baumannii WHG40004 to its lytic phage P21 and thereafter isolated a phage-resistant bacterial mutant, named Ev5-WHG. We then aimed to identify potential agents to aid phage killing of Ev5-WHG by analyzing its genome and that of the wild-type strain. The enriched Gene Ontology (GO) analysis based on genetic alterations in minor alleles and mutations showed that pathways such as zinc ion transport and cell membrane synthesis could play certain roles in phage resistance. Remarkably, the combination of zinc acetate and P21 showed increased bactericidal effect on Ev5-WHG. Significantly also, we showed that P21 completely prevented the growth of wild-type WHG40004 in the presence of antibiotics (meropenem and imipenem). The results from this study indicate that the analysis of phage resistance signatures during adaptation of bacteria to a lytic phage can inform the choice of agents to work cooperatively with phage to limit and/or reverse resistance. This approach could be important for guiding future successful phage therapy.IMPORTANCE Bacteriophages have proven very useful as alternative therapeutic agents in combating multidrug-resistant bacterial infections; however, bacterial resistance to phages threatens their use. In this study, we showed a new strategy of leveraging genetic signatures that accompany phage resistance in bacteria to predict agents that can be used with lytic phages to combat multidrug-resistant Acinetobacter baumannii. Significantly, this approach was helpful in suggesting the use of zinc acetate to reduce resistance in phage-resistant bacteria, as well as the use of phage with antibiotics meropenem and imipenem to prevent resistance in a wild-type strain of multidrug-resistant A. baumannii. The approach of this study will be helpful for improving the outcome of phage therapy and in overcoming antimicrobial resistance.
研究领域:
微生物学
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基因组学
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抗菌素耐药性
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噬菌体疗法
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细菌遗传学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Weilun Pan,Bodeng Wu,Chengtao Nie,Tingting Luo,Zhenli Song,Jie Lv,Yong Tan,Chunchen Liu,Mingzhen Zhong,Tong Liao,Zhenxun Wang,Guanghui Yi,Limin Zhang,Xiaoliu Liu,Bo Li,Jinxiang Chen,Lei Zheng
Developing an effective dressing against bacterial infection and synchronously addressing wound complications, such as bleeding, long-term inflammation, and reinfection, are highly desirable in clinical practice. In this work, a second near-infrared (NIR-II) responsive nanohybrid consisting of imipenem encapsulated liposome with gold-shell and lipopolysaccharide (LPS)-targeting aptamer, namely ILGA, is constructed for bacteria elimination. Benefiting from the delicate structure, ILGA exhibits strong affinity and a reliable photothermal/antibiotic therapeutic effect toward multidrug-resistant Pseudomonas aeruginosa (MDR-PA). Furthermore, by incorporating ILGA with a thermosensitive hydrogel poly(lactic-co-glycolic acid)–polyethylene glycol–poly(lactic-co-glycolic acid) (PLGA-PEG-PLGA), a sprayable dressing ILGA@Gel was prepared, which enables a quick on-demand gelation (10 s) for wound hemostasis and offers excellent photothermal/antibiotic efficacy to sterilize the infected wound. Additionally, ILGA@Gel provides satisfactory wound-healing environments by reeducating wound-associated macrophages for inflammation alleviation and forming a gel layer to block exogenous bacterial reinfection. This biomimetic hydrogel reveals excellent bacteria eradication and wound recovery effectiveness, demonstrating its promising potential for managing complicated infected wounds.
研究领域:
生物医学工程
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纳米技术
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药学
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伤口愈合
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传染病
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材料科学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Zhihui Cai,Jinjin He,Jun Jiang,Zihan Zhao,Ye Shu
Background Sepsis is one of the major threats to human health with high mortality. Simiao Yong'an decoction (SMYAD) has the efficacy of anti-inflammation, improving coagulation and microcirculation, which is applicable for the clinical assistance treatment of sepsis . Yet, its material basis and relevant mechanisms are still vague. Purpose Explore the quality markers (Q-markers), biomarkers and potential mechanisms of SMYAD combined with imipenem/cilastatin sodium for anti-sepsis. Methods Linear-Trap-LC/MS n was employed to profile the compounds in the extract and medicated serum of SMYAD. Then, the components and targets obtained from databases were applied to network pharmacology. Q-markers’ range was narrowed via the affinity of three times docking and determined as per its screening criteria. Also, the content of them was detected by HPLC. Next, cecal ligation and puncture (CLP) model was reproduced to observe the effect of SMYAD united antibiotic by survival rate, histopathology score, ELISA, western blot and qPCR. Finally, metabolomics based upon GC–MS was exerted to discover the differential endogenous metabolites, metabolic pathway and joint pathway of SMYAD combined with antibiotic for sepsis. Results The 25 serum migrant ingredients derived from 113 chemical compounds of SMYAD were identified for the first time, and 6 components were determined as the Q-markers of SMYAD. The enrichment analysis indicated that the potential mechanism was mainly associated with the IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway. Then, SMYAD united antibiotic declined the mortality of septic rats, restored cytokine levels, ameliorated histopathological lesions and decreased the mRNA and protein expression of target proteins in a dose-dependent way. Furthermore, 8 differential metabolites were regarded as latent biomarkers related to the antiseptic effect of SMYAD united antibiotic, which were mainly involved in the Citrate cycle (TCA cycle) metabolic pathway. Conclusions Different skeletons of compounds, including iridoids, phenylpropanoids, organic acids, triterpenes and others, were the main compositions of SMYAD. Among them, 6 components were determined as the Q-markers, which provided a basis for the construction of quality standards for this ancient classic formula. The combination therapy of SMYAD and antibiotic obviously ameliorated inflammatory reaction, coagulation dysfunction and microcirculation abnormalities for sepsis by inhibiting IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway.
研究领域:
药理学
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中医药
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感染性疾病
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分子生物学
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代谢组学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CLINICAL MICROBIOLOGY
·
2024
·Vol. 62
·期 2
·
IF 6.1
Zhimin Lu,Xiaonan Wang,Licai Ma,Leina Dou,Xiangjun Zhao,Jin Tao,Yang Wang,Shaolin Wang,Dejun Liu,Yingbo Shen,Xuezhi Yu,Wenbo Yu,Liangxi Jia,Zhanhui Wang,Jianzhong Shen,Kai Wen
Rapid phenotypic detection assays, including Carba NP and its variants, are widely applied for clinical diagnosis of carbapenemase-producing Enterobacterales (CPE). However, these tests are based on the acidification of the pH indicator during carbapenem hydrolysis, which limits test sensitivity and speed, especially for the detection of CPE producing low-activity carbapenem (e.g., OXA-48 variants). Herein, we developed a novel rapid and sensitive CPE detection method (Carba PBP) that could measure substrate (meropenem) consumption based on penicillin-binding protein (PBP). Meropenem-specific PBP was used to develop a competitive lateral flow assay (LFA) for meropenem identification. For the detection of carbapenemase activity, meropenem concentration was optimized using a checkerboard assay. The performance of Carba PBP was evaluated and compared with that of Carba NP using a panel of 94 clinical strains characterized by whole-genome sequencing and carbapenem susceptibility test. The limit of detection of PBP-based LFA for meropenem identification was 7 ng mL−1. Using 10 ng mL−1 meropenem as the substrate, Carba PBP and Carba NP could detect 10 ng mL−1 carbapenemase within 25 min and 1,280 ng mL−1 CPE in 2 h, respectively. The sensitivity and specificity were 100% (75/75) and 100% (19/19) for Carba PBP and 85.3% (64/75) and 100% (19/19) for Carba NP, respectively. When compared with Carba NP, Carba PBP showed superior performance in detecting all the tested CPE strains (including OXA-48-like variants) within 25 min and presented two orders of magnitude higher analytical sensitivity, demonstrating potential for clinical diagnosis of CPE.
研究领域:
微生物学
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临床诊断
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分子生物学
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传染病
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yuwei Zheng,Jiaying Chi,Jiayu Ou,Ling Jiang,Liqing Wang,Rui Luo,Yilang Yan,Zejun Xu,Tingting Peng,Jianfeng Cai,Chuanbin Wu,Peng Teng,Guilan Quan,Chao Lu
The development of narrow-spectrum antimicrobial agents is paramount for swiftly eradicating pathogenic bacteria, mitigating the onset of drug resistance, and preserving the homeostasis of bacterial microbiota in tissues. Owing to the limited affinity between the hydrophobic lipid bilayer interior of bacterial cells and most hydrophilic, polar peptides, the construction of a distinctive class of four-armed host-defense peptides/peptidomimetics (HDPs) is proposed with enhanced specificity and membrane perturbation capability against Pseudomonas aeruginosa by incorporating imidazole groups. These groups demonstrate substantial affinity for unsaturated phospholipids, which are predominantly expressed in the cell membrane of P. aeruginosa , thereby enabling HDPs to exhibit narrow-spectrum activity against this bacterium. Computational simulations and experimental investigations have corroborated that the imidazole-rich, four-armed peptidomimetics exhibit notable selectivity toward bacteria over mammalian cells. Among them, 4H10, characterized by its abundant and densely distributed imidazole groups, exhibits impressive activity against various clinically isolated P. aeruginosa strains. Moreover, 4H10 has demonstrated potential as an antibiotic adjuvant, enhancing doxycycline accumulation and exerting effects on intracellular targets by efficiently disrupting bacterial cell membranes. Consequently, the hydrogel composed of 4H10 and doxycycline emerged as a promising topical agent, significantly diminishing the skin P. aeruginosa burden by 97.1% within 2 days while inducing minimal local and systemic toxicity.
研究领域:
微生物学
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药理学
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生物化学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2025
·
IF 11.3
Wenyan Jiang,Shan Zhang,Chen Xu,Haojie Sun,Ziye Xing,Xiao Liang,Hongming He,Quanshun Li
The prevalence of antibiotics in natural aquatic environment has become an emerging class of organic pollutants, impacting both aquatic ecosystems and human health. Herein, spherical mesoporous covalent organic frameworks (SMCOF) was successfully synthesized and employed in the immobilization of OXA-48 β-lactamase through pore adsorption, in which 1,3,5-tris(4-aminophenyl)benzene and 2,5-dimethoxyterephthalaldehyde were utilized as the node and linker, respectively. Structural characterization demonstrated that OXA-48 was successfully adsorbed into the pores of SMCOF, achieving a loading capacity of 546.81 mg/g. Meanwhile, OXA-48@SMCOF maintained the catalytic activity of 62.08 % and 104.98 % after the treatment at 50 °C (pH of 7.4) and 37 °C (pH of 11) for 30 min, respectively. Further, all the catalytic activities of OXA-48@SMCOF remained above 88 % after the incubation in the presence of various organic solvents or proteinase K for 1 h. Moreover, OXA-48@SMCOF retained 53.78 % and 41.18 % of original activity after 15 cycles of reuse and 10 days of storage, respectively, indicating its favorable reusability and storage stability. In the application of degrading antibiotics in lake water samples, OXA-48@SMCOF demonstrated superior degradation performance compared to free OXA-48, attributing to the protective effect of SMCOF. Overall, the present study provides a promising technique to construct high performance immobilized enzymes, which is beneficial for the future application of OXA-48@SMCOF in the degradation of antibiotics during water treatment process.
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Yongtian Yuan,Liangliang Zhao,Zhuchun Bei,Baogang Wang,Dongna Zhang,Likun Xu,Jiahui Liu,Meng Lv,Qin Xu,Yabin Song
Introduction: Drug-resistant bacteria, particularly Acinetobacter baumannii, present a significant threat to global public health, highlighting the urgent need for novel antibacterial therapies. Drug repurposing has emerged as a promising strategy to accelerate therapeutic development by identifying new applications for existing pharmaceuticals. This study investigates the potential of naphthoquine phosphate (NQP), an antimalarial agent, as a broad-spectrum antibacterial candidate against the multidrug-resistant strain A. baumannii LAC-4.Methods: To evaluate the antibacterial activity of NQP, we determined the minimum inhibitory concentration (MIC) against Acinetobacter baumannii LAC-4. Inhibition kinetics were analyzed to assess concentration-dependent effects. Membrane permeability assays were performed to examine NQP-induced changes in cell membrane integrity. Oxidative damage tests were conducted to investigate impacts on bacterial metabolic processes. Morphological changes in A. baumannii LAC-4 treated with NQP of MIC were observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Additionally, transcriptome analysis was performed to identify disrupted physiological pathways associated with NQP exposure.Results and discussion: NQP exhibited broad-spectrum antibacterial activity, with a MIC of 62.5 μg/mL against Acinetobacter baumannii LAC-4. Its inhibition kinetics curve confirmed a concentration-dependent inhibitory effect. Membrane permeability tests revealed that NQP disrupts cell membrane integrity, enhancing permeability—consistent with TEM/SEM observations showing significant structural damage in NQP-treated A. baumannii, including membrane rupture, cellular deformation, and cytoplasmic disorganization. Oxidative damage tests indicated NQP impacts bacterial metabolism, and transcriptome analysis further demonstrated that NQP disrupts multiple physiological pathways, primarily through enhanced membrane permeability and induced oxidative stress. These findings support NQP as a promising molecular scaffold for developing novel therapies against Acinetobacter baumannii infections, highlighting its potential in drug repurposing strategies for combating drug resistance.
研究领域:
微生物学
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药理学
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抗菌素耐药性
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细胞生物学
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分子生物学
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药物再利用
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular and Infection Microbiology
·
2025
·
IF 4.8
Jiansheng Lin,Chunyan Lin,Jingyang Zheng
Background: P. diazotrophicus was isolated from a newborn with D-galactosemia complicated sepsis. A homologous blaCAR-2 gene, encoding CAR-2, a predicted member of the CAR family subclass B3 metallo-β-lactamases (MBLs), was found in the genome of this strain. This study aimed to explore the identification of a novel CAR-2 protein encoded by the chromosome of P. diazotrophicus Pd1 that exhibits the zinc-binding motifs of subclass B3 enzymes and the regulatory pattern of CARR, located directly upstream of the blaCAR-2 gene, on the blaCAR-2 gene and its impact on antibiotic resistance.Methods: Antibiotic susceptibility testing was conducted by the plate agar dilution method. Site-directed mutagenesis was conducted using Mut Express II Fast Mutagenesis Kit V2. Kinetic assays were used to determine the hydrolysis of β-Lactam. The construction of bacterial knockout strains was carried out according to the principle of homologous recombination. The detection of the mRNA expression level of the gene was performed by Real-time Quantitative PCR (qPCR).Results: The minimum inhibitory concentrations (MICs) for E.coli DH5α(pHSG398::CAR-2), which expressed blaCAR-2, increased significantly for cefalothin, cefuroxime and cefotaxime sodium by 2-, 16- and 32- fold, respectively, which showed that blaCAR-2 had resistance to these three antibiotics. This protein, which was a MBL, contains two classical zinc-binding sites characteristic of subclass B3, with the amino acid motif His136, His138, His211, Asp140, His141, and His276. Among the six residues, His136, Asp140, and His211 exhibited the highest catalytic activity. We determined that CAR-2 can effectively hydrolyze cefalothin, cefuroxime and cefotaxime. The chloramphenicol resistance of the constructed E. coli DH5α strain was significantly reduced in the presence of CARR than in the absence of CARR. Compared with those for the wild-type P. diazotrophicus, MICs of cefalothin, cefuroxime and cefotaxime for the ΔCARR strain increased by 8-, 8- and 16-fold, respectively, and the expression level of blaCAR-2 also increased by approximately 10-fold.Conclusion: Overall, CAR-2 is a novel subclass B3 MBL of the CAR family that exhibits catalytic activity against cefalothin, cefuroxime and cefotaxime. CARR represses the expression of blaCAR-2, thereby reducing the resistance of P. diazotrophicus to these antibiotics. This provided a theoretical basis for revealing new mechanisms of pathogen resistance.
研究领域:
微生物学
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分子生物学
·
感染性疾病
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抗生素耐药机制
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基因调控
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Shuting Xie,Ri He,Qifan Zhu,Mingliang Jin,Ruizhi Yang,Shitao Shen,Jiayi Cui,Yiying Zou,Minmin Zhang,Lingling Shui
A sessile droplet array of 4’-pentyl-biphenyl-4-carboxylic acid (PBA) doped 5CB sessile droplets (12 −104 µm) is prepared by inkjet printing and applied for label-free sensing of penicillin G according to the configuration transition from axial to windmill based on the molecular alignment of 5CB at the LC-aqueous interface. Selective determination of penicillin G is achieved according to the target-selective enzymatic hydrolysis catalyzed by penicillinase, exhibiting sensitive detection and fast response with a detection limit of 0.178 ng/mL within 3–5 min. The sensitivity is linear depending on LC droplet size. Under the optimized conditions, the linear detection range is 1.78–178.0 ng/mL. Such a droplet array sensor has also been successfully applied to determine penicillin G in real river and lake water samples with RSD of 102–119%. Such a platform possesses the advantages of simple and cheap construction of an ordered array for multiplex sensing, and easy characterization via a polarizer . The quantification range of this proposed label-free optical penicillin G sensor covers the maximum residue limits in raw milk and river water defined in the European Union Regulation, and thus being applicable for food and environmental monitoring. By engineering LC-based probes, this approach could be extended to sense various molecules and ions in biomedical and chemical scenarios. And the sessile droplets on polymer substrates would also bring the possibility for employing in flexible and wearable devices in the future.
研究领域:
光学传感
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分析化学
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环境监测
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR & CELLULAR PROTEOMICS
·
2022
·Vol. 21
·期 9
·
IF 7.381
Lishan Zhang,Zujie Yao,Huamei Tang,Qingli Song,Huanhuan Song,Jindong Yao,Zhen Li,Xiaofang Xie,Yuexu Lin,Xiangmin Lin
Protein lysine acetylation (Kac) modification plays important roles in diverse physiological functions. However, there is little evidence on the role of Kac modification in bacterial antibiotic resistance. Here, we compared the differential expressions of whole-cell proteins and Kac peptides in oxytetracycline sensitive and oxytetracycline resistance (OXYR) strains of Aeromonas hydrophila using quantitative proteomics technologies. We observed a porin family protein Aha1 downregulated in the OXYR strain, which may have an important role in the OXY resistance. Interestingly, seven of eight Kac peptides of Aha1 decreased abundance in OXYR as well. Microbiologic assays showed that the K57R, K187R, and K197R Aha1 mutants significantly increased antibiotic resistance to OXY and reduced the intracellular OXY accumulation in OXY stress. Moreover, these Aha1 mutants displayed multidrug resistance features to tetracyclines and β-lactam antibiotics. The 3D model prediction showed that the Kac states of K57, K187, and K197 sites located at the extracellular pore vestibule of Aha1 may be involved in the uptake of specific types of antibiotics. Overall, our results indicate a novel antibiotic resistance mechanism mediated by Kac modification, which may provide a clue for the development of antibiotic therapy strategies.
研究领域:
微生物学
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药理学
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分子生物学
✓ 已验证
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）