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
·
传染病学
·
药物开发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIO-MEDICAL MATERIALS AND ENGINEERING
·
2017
·Vol. 28
·期 4
·339-345
·
IF 0.7
Bai Ningning,Tan Cui,Li Qing,Xi Zhongxian
In this paper, a low-cost and multifunctional hydroxyapatite (HA)/pefloxacin (PFLX) drug eluting layer is coated on magnesium (Mg) alloy through a simple hydrothermal and dip process. The drug PFLX could provide effective prevention for bone infection and inflammation due to its broad-spectrum antibacterial property. And HA would promote the growth of new bone and further improve the biocompatibility of implants. Besides, both PFLX and HA exhibits excellent corrosion protection for Mg alloy substrate. This coating is of great value for improving the application of Mg alloy as biomaterials.
研究领域:
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bio-Design and Manufacturing
·
2024
·
IF 8.1
Li Zhentao,Song Ting,Jiao Yanpeng,Zhu Zijing,Liao Yang,Liu Zonghua
The low temperature, high salt content, and bacterial composition of a seawater environment can induce severe infections in open wounds, thus impending wound healing. To date, numerous wound dressings have been developed to injuries and various antibacterial functions. However, ordinary antibacterial strategies could not provide long-term resistance to infections and could not promote wound healing. Here, we proposed a strategy for enhancing resistance to seawater immersion wound infection by killing bacteria and delivering bacterial antigens in situ. Specifically, MXene-embedded tannin–Eu 3+ (M@TA–Eu) particles were constructed to effectively alleviate injuries infected through seawater immersion and persistently fight infection by forming in situ bacterial vaccines and immune memory. In the particle, the platform composed of TA and Eu 3+ exhibited provascularization and antigen presentation effects. MXenes with near-infrared photothermal effect were introduced to kill the bacteria, promote the recruitment of antigen presentation cells, and ultimately enhance vaccination efficacy. Experimental results showed that the particles not only effectively accelerated the healing of injuries by relieving wound inflammation and inhibiting bacteria but also produced a potent vaccination by forming in situ bacterial vaccines. Therefore, the M@TA–Eu particles are novel materials for high-grade anti-infection dressing.
研究领域:
生物医学工程
·
免疫学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Jianqiang Huang,Jingran Sun,Ling Pan,Fuping Song,Huiqin Huang,Kunlian Mo,Yan Wang,Yonghua Hu
Micropterus salmoides , a freshwater fish of significant economic value, faces substantial challenges due to frequent infection by Aeromonas veronii and excessive antibiotic use. Bacillus tequilensis emerges as a promising antibiotic alternative, enhancing fish immunity and gut health. However, its specific effects on M. salmoides have not been fully clarified. This study examined the impact of different concentrations of B. tequilensis Bt-CO (0, 6.0 × 10 9 , 6.0 × 10 10 , and 6.0 × 10 11 CFU/kg) on juvenile M. salmoides , focusing on growth, survival, body indexes, immune and antioxidant responses, digestive enzymes, disease resistance, intestinal microbiota, and metabolism. Following an 8-week feeding trial, Bt-CO had no significant impact on the growth performance, hepatosomatic index, and condition factor of M. salmoides . However, at a concentration of 6.0 × 10 11 CFU/kg, it significantly enhanced immune indicators, glutathione peroxidase activity, digestive enzyme activities, and post- A. veronii infection survival rates of M. salmoides . Gut microbiota analysis revealed that Bt-CO enhanced beneficial bacteria while reducing harmful ones. Metabolomic analyses indicated that Bt-CO modulated intestinal metabolite levels, including SM(d16:1/24:1(15Z)), d -Threitol, and PC(18:1(9Z)/P-16:0), involving 25 metabolic pathways like d -Glutamine and D-glutamate metabolism. Correlation analysis highlighted significant links between specific gut bacteria and differential metabolites. Overall, this study suggests that incorporating Bt-CO at a concentration of 6.0 × 10 11 CFU/kg in the diet of juvenile M. salmoides could: (i) improve intestinal health by modulating microbial composition and metabolite profile in the intestine; and (ii) enhance fish digestive capacity, immunity, and disease resistance.
研究领域:
微生物学
·
免疫学
·
水产养殖
·
代谢组学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 23
·4735-4745
·
IF 6.331
Minqi Wang,Yiqi Yang,Guanghao Chi,Kai Yuan,Feng Zhou,Liang Dong,Haibei Liu,Qinghui Zhou,Weihua Gong,Shengbing Yang,Tingting Tang
Large bone defects face a high risk of infection, which can also lead to bone homeostasis disorders. This seriously hinders the bone healing process; therefore, the help of a dual-functional scaffold that has both anti-infection and bone-homeostasis-regulating capacities is needed in the treatment of infected bone defects. In this study, a 3D printed dual-functional scaffold composed of poly-ε-caprolactone (PCL), mesoporous bioactive glasses (MBG), and gallium (Ga) was produced. In vitro experiments demonstrated the excellent antibacterial ability of the PCL/MBG/Ga scaffold against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli). The scaffold also significantly inhibited osteoclastic activity and promoted osteogenic differentiation. Furthermore, a rabbit model with an infected bone defect in the radius was used to evaluate the in vivo bone healing capability of PCL/MBG/Ga. The results demonstrate that the PCL/MBG/Ga scaffold can significantly accelerate bone healing and prevent bone resorption, suggesting its potential for application in repairing infected bone defects.
研究领域:
生物材料学
·
骨科医学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
·
2024
·
IF 7.1
Lei He,Yongze Liu,Haomiao Zhu,Feng Chen,Jiong Shi,Panpan Song,Fuqi Feng,Juqing Cui,Xiaofeng Ma,Jun Zhang
Nasal diseases are pervasive infections that can impair the quality of life of sufferers. In this study, a flexible modified triplochitin scleroxylon (MTS)-based Janus hydrogel (MTS@P/DLT) was obtained by disrupting the homogeneity of the system using DL-α-tocopherol (DLT) with flexible wood as the framework and poly(vinyl alcohol) (PVA) as the outer matrix. At a PVA concentration of 10 wt %, DLT formed a homogeneous layer, as revealed by electron microscopy. Mechanical property analysis showed that chemical and hydrogel modifications significantly increased the flexibility and toughness of the hydrogel. Microscopic and macroscopic assessment of the characteristics of the two sides of the MTS@P/DLT hydrogel revealed that one side of the DLT film had antiadhesion effects. Molecular dynamics simulation was used to determine the movement law of DLT in a PVA solution. The stronger intermolecular force between DLT and PVA than that between DLT and water, as well as between DLT molecules, enabled the formation of a homogeneous DLT film by controlling the concentration of PVA. In vitro and in vivo models demonstrated the potential of MTS@P/DLT to resist infection and facilitate recovery. Thus, MTS@P/DLT is promising for medical use.
研究领域:
材料科学
·
医学
·
生物工程
✓ 已验证
产品关联
DOI
高影响因子
EBioMedicine
·
2024
·
IF 9.7
Shuying Chen,Yahui Xiong,Fan Yang,Yanke Hu,Jinghao Feng,Fei Zhou,Zhonghua Liu,Hengdeng Liu,Xiaogang Liu,Jingling Zhao,Zhaoqiang Zhang,Lei Chen
Background
Severe burn wounds face two primary challenges: dysregulated cellular impairment functions following infection and an unbalanced wound hydration microenvironment leading to excessive inflammation and collagen deposition. These results in hypertrophic scar contraction, causing significant deformity and disability in survivors.
Methods
A three-dimensional (3D) printed double-layer hydrogel (DLH) was designed and fabricated to address the problem of scar formation after burn injury. DLH was developed using methacrylated silk fibroin (SFMA) and gelatin methacryloyl (GelMA) for the upper layer, and GelMA and hyaluronic acid methacryloyl (HAMA) for the lower layer. To combat infection, copper-epigallocatechin gallate (Cu-EGCG) was incorporated into the lower layer bioink, collectively referred to as DLS. To balance wound hydration levels, HaCaT cells were additionally encapsulated in the upper layer, designed as DLS/c.
Findings
DLH demonstrated suitable porosity, appropriate mechanical properties, and excellent biocompatibility. DLS exhibited potent antimicrobial properties, exerted anti-inflammatory effects by regulating macrophage polarisation, and may enhance angiogenesis through the HIF-1α/VEGF pathway. In the DLS/c group, animal studies showed significant improvements in epidermal formation, barrier function, and epidermal hydration, accompanied by reduced inflammation. In addition, Masson’s trichrome and Sirius red staining revealed that the structure and ratio of dermal collagen in DLS/c resembled that of normal skin, indicating considerable potential for scarless wound healing.
Interpretation
This biomimetic matrix shows promise in addressing the challenges of burn wounds and aiming for scarless repair, with benefits such as anti-infection, epidermal hydration, biological induction, and optimised topological properties.
研究领域:
生物材料学
·
再生医学
·
创伤修复
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2012
·
IF 2.686
Shen Liu,Jingwen Zhao,Hongjiang Ruan,Wei Wang,Tianyi Wu,Wenguo Cui,Cunyi Fan
The complications of tendon injury are frequently compromised by peritendinous adhesions and tendon sheath infection. Physical barriers for anti-adhesion may increase the incidence of postoperative infection. This study was designed to evaluate the potential of silver nanoparticles (AgNPs)-loaded poly( l -lactide) (PLLA) electrospun fibrous membranes to prevent adhesion formation and infection. Results of an in vitro drug release study showed that a burst release was followed by sustained release from electrospun fibrous membranes with a high initial silver content. Fewer fibroblasts adhered to and proliferated on the AgNP-loaded PLLA electrospun fibrous membranes compared with pure PLLA electrospun fibrous membrane. In the antibacterial test, the AgNP-loaded PLLA electrospun fibrous membranes can prevent the adhesion of Gram-positive Staphylococcus aureus and Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa . Taken together, these results demonstrate that AgNP-loaded PLLA electrospun fibrous membranes have the convenient practical medical potential of reduction of infection and adhesion formation after tendon injury.
研究领域:
生物材料学
·
组织工程学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 11
·2697-2708
·
IF 6.331
Fanjun Zhang,Cheng Hu,Li Yang,Kunpeng Liu,Yao Ge,Yuan Wei,Jingyu Wang,Rifang Luo,Yunbing Wang
Hospital-acquired infections and thrombosis caused by bacteria attached to the device surface, or fibrin crosslinking owing to platelet accumulation/activation, are major healthcare challenges that cause morbidity and mortality. To prevent these, surface coating technologies are considered an efficient tool that can combine hemocompatibility and bactericidal activity. In this study, surface-initiated polymerization was conducted to form an all-in-one hydrogel coating that could adapt to diverse medical devices. Different monomer ratios (acrylamide/acrylic acid) were used to adjust the antimicrobial agent loading capacity. The hydrogel coating obtained by a simple dip-absorbing method showed good hemocompatibility and maintained efficient bactericidal activity. We also explored the loading and release of antimicrobial agents with different molecular sizes, including nano-Ag particles, antibiotics, and antimicrobial peptides. The inhibition zone test and confocal laser scanning microscopy revealed that the hydrogel coating could maintain remarkable antimicrobial and antifouling properties for four weeks. Furthermore, the hydrogel coating decreased the platelet adhesion/activation without risk of hemolysis. The ex vivo blood circulation study confirmed the antithrombotic properties of the hydrogel coating. Such all-in-one hydrogel coatings that maintain high cell viability and exhibit both hemocompatibility and bactericidal activity possess the potential for applications in blood-contacting devices.
研究领域:
生物医学工程
·
材料科学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2020
·Vol. 18
·期 1
·1-15
·
IF 6.518
Zhang Man,Ye Lili,Huang Hao,Cheng Dandan,Liu Kaixin,Wu Wenbo,Shen Fukui,Jiang Zhihong,Hou Yuanyuan,Bai Gang
Background Nanoparticle-based pulmonary drug delivery systems are commonly developed and applied for drug-targeted delivery. They exhibit significant advantages compared to traditional pulmonary drug delivery systems. However, developing the formulation of each drug is a time-consuming and laborious task.Results In this study, a universal lung-targeting nanoparticle was designed and constructed. The self-assembled micelles were composed of a platycodon secondary saponin, 3-O-β-d-glucopyranosyl platycodigenin 682 (GP-682), based on its specific amphiphilic structure. The GP-682 micelles exhibited a relatively stable zeta potential with a particle size between 60 and 90 nm, and the critical micelle concentration (CMC) value was approximately 42.3 μg/mL. Preincubation of GP-682 micelles markedly enhanced their cell membrane permeability and improved drug uptake in vitro. The results were visualized using fluorescent dye tracing, transmission electron microscopy (TEM) observations and the lactate dehydrogenase (LDH) release assay. The obtained benefits enhanced the distribution of levofloxacin (Lev) in mouse lung tissue and reduced antibiotics overdosing. The acute lung injury mouse model induced by the Pseudomonas aeruginosa PA 14 strain demonstrated that preinjection of GP-682 micelles before antibiotic administration resulted in a higher survival rate and anti-infective efficacy in vivo. It also caused reductions in pulmonary injury, bacterial invasion and cytokine expression compared with treatment with Lev alone.Conclusion sGP-682 micelles are another nanoparticle-based pulmonary drug delivery system and provide a new lung-targeting therapy option.
研究领域:
药学
·
纳米医学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Xinqi Zheng,Pengran Guo,Yue Zhang,Jingwei Xu,Jian Sun,Yongqian Lei
The environmental pollution and human health risks caused by anti-infective residual drugs in the environment have attracted much attention. More convenient and effective detection methods to achieve the rapid and high sensitivity detection for such pollutants are required. In this work, a novel surface-enhanced Raman scattering (SERS) strategy based on vortex aggregation of AgNPs was proposed for the detection of anti-infective drugs in environmental water. The method enhanced the Raman signal of the targets by 2–7.4 times. The mechanism of aggregation enhancement effect under the low-frequency oscillation procedure which significantly enhanced the SERS signal of targets molecular on the aggregated AgNPs was revealed by UV–vis and ICP-MS methods. Three drugs of cefazolin sodium, pefloxacin , and chloroquine phosphate were determined. The detect limits were 3.97 × 10 −9 mol/L, 2.42 × 10 −10 mol/L, and 7.34 × 10 −9 mol/L for cefazolin sodium, pefloxacin, and chloroquine phosphate, respectively. The quantitative relationships were obtained in a wide linear range of 4–5 orders as well as good accuracy and stability with the recoveries of 84.0%–97.1% and the relative standard deviations (RSDs) less than 4.6% for spiked in actual water samples. This method also had excellent repeatability and stability, which have potential application for rapid detection of trace pollutants in water environment.
研究领域:
环境科学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Zesong Ruan,Tingwang Shi,Zhao Guo,Yu Zhu,Wenbo Wang,Yihong Ma,Cheng Ding,Yunlong Zhang,Xiaojun Wang,Yunfeng Chen,Han Lin,Min Ge
Biofilm infection microenvironment (BIM) in orthopedic implant-associated infections forms a robust barrier that resists antimicrobial agents and evades the host's immune system, yet there are currently limited effective targeted therapies against the characteristics of the BIM. Here, an emerging nanocatalytic immunotherapy strategy is proposed for treatment based on microenvironmental oxygen regulation. It is reported that the light-activated oxygen immune regulators (LAOIR) can effectively target and disrupt biofilms in the initial phase of phototherapy by generating singlet oxygen (¹O₂). The LAOIR-induced hypoxic microenvironment prolongs neutrophil lifespan and mitigates the immune tolerance induced by lipoteichoic acid (LTA) caused by killed bacteria. As the biofilm disintegrates and oxygen recovers, the neutrophil “immune switch” is triggered, and neutrophils are exhibited enhanced bactericidal activity during immune training with LTA exposure, such as NETosis and phagocytosis. Meanwhile, LAOIR therapy mediates neutrophils to express increased levels of proinflammatory cytokines IL-6, IL-1β, and the chemokine receptors CCR2 and CXCR2, promoting immune recruitment and resulting in a more robust therapeutic effect compared to vancomycin. In vitro and in vivo experiments have demonstrated that LAOIR outperform clinical antibiotics in the treatment of bacterial infections, providing direct evidence for the utilization of oxygen-modulated immune response strategies in the treatment of orthopedic implants.
研究领域:
生物医学工程
·
免疫学
·
微生物学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）