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Scientific Reports · 2025 ·Vol. 15 ·期 1 ·1-11 · IF 3.9

Antibiofilm activity of Plumbagin against Staphylococcus aureus

Bie Songtao,Yuan Hui,Shi Chen,Li Chunshuang,Lu Ming,Yao Ze,Liu Ruobing,Lu Ding,Ma Tenglong,Yu Heshui

In chronic infections caused by Staphylococcus aureus , biofilm is a major virulence factor. In Staphylococcus aureus biofilms, bacteria are embedded in a matrix of extracellular polymeric substances and are highly tolerant to antimicrobial drugs. However, the lack of effective solutions to inhibit biofilm formation remains a challenge, and the mechanism of inhibition of biofilm formation targeting extracellular polymeric substances is unclear. The aim of the present study was to investigate the inhibitory mechanisms of Plumbagin against Staphylococcus aureus biofilms formation by affecting secretion of extracellular polymeric substances using the high-content screening. Our results showed Plumbagin (16 µg/mL) inhibited biofilm formation, revealing a significant reduction in both biomass and bacterial metabolic activity, and disrupted the biofilm structure, leading to a significant decrease in both biological volume and average thickness ( P  ≤ 0.01). High-content screening imaging indicated that the Plumbagin treatment induced alterations in the extracellular polymeric substances of Staphylococcus aureus biofilm, significantly reducing the quantities of extracellular polysaccharide, proteins and extracellular DNA. Interestingly, extracellular DNA within the matrix was found to be the most sensitive to Plumbagin treatment. Extracellular DNA formation was significantly inhibited at a concentration of 4 µg/mL, whereas the inhibition of extracellular polysaccharide and proteins required a higher concentration of 8 µg/mL. Overall, these results demonstrated the inhibitory effects of Plumbagin on Staphylococcus aureus biofilm formation and extracellular polymeric substances secretion, suggesting that extracellular DNA may be a potential target for the anti-biofilm activity of Plumbagin. These findings will provide new insights into the mode of action of Plumbagin in treating infections caused by Staphylococcus aureus biofilms.

CAS / MDL: 56-81-5 1440964-89-5
研究领域: 微生物学 · 药理学 · 感染病学
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CHINESE JOURNAL OF POLYMER SCIENCE · 2018 ·Vol. 36 ·期 5 ·576-583 · IF 2.016

A Biomimetic Surface for Infection-resistance through Assembly of Metal-phenolic Networks

Jiang Ru-Jian,Yan Shun-Jie,Tian Li-Mei,Xu Shi-Ai,Xin Zhi-Rong,Luan Shi-Fang,Yin Jing-Hua,Ren Lu-Quan,Zhao Jie

Despite the fact that numerous infection-resistant surfaces have been developed to prevent bacterial colonization and biofilm formation, developing a stable, highly antibacterial and easily produced surface remains a technical challenge. As a crucial structural component of biofilm, extracellular DNA (eDNA) can facilitate initial bacterial adhesion, subsequent development, and final maturation. Inspired by the mechanistic pathways of natural enzymes (deoxyribonuclease), here we report a novel antibacterial surface by employing cerium (Ce(IV)) ion to mimic the DNA-cleavage ability of natural enzymes. In this process, the coordination chemistry of plant polyphenols and metal ions was exploited to create an in situ metal-phenolic film on substrate surfaces. Tannic acid (TA) works as an essential scaffold and Ce(IV) ion acts as both a cross-linker and a destructor of eDNA. The Ce(IV)-TA modified surface exhibited highly enhanced bacteria repellency and biofilm inhibition when compared with those of pristine or Fe(III)-TA modified samples. Moreover, the easily produced coatings showed high stability under physiological conditions and had nontoxicity to cells for prolonged periods of time. This as-prepared DNA-cleavage surface presents versatile and promising performances to combat biomaterial-associated infections.

CAS / MDL: 16774-21-3 10025-77-1
研究领域: 生物材料学 · 医学工程 · 微生物学
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BIOMATERIALS · 2019 · IF 10.273

A series of MOF/Ce-based nanozymes with dual enzyme-like activity disrupting biofilms and hindering recolonization of bacteria

Zhengwei Liu,Faming Wang,Jinsong Ren,Xiaogang Qu

Notorious bacterial biofilms are becoming severe threats to public health worldwide. As the important component in biofilm extracellular polymeric substances (EPS), extracellular DNA (eDNA) has been manifested to connect different EPS components and bacteria together, leading biofilms hard to eliminate. Herein a series of MOF/Ce-based nanozymes with deoxyribonuclease (DNase) and peroxidase mimetic activities have been designed and synthesized for combating biofilms. The cerium (IV) complexes (DNase mimics) are capable of hydrolyzing eDNA and disrupting established biofilms, while the MOF with peroxidase-like activity can kill bacteria exposed in dispersed biofilms in the presence of H 2 O 2 . This can avoid the recolonization of bacteria and recurrence of biofilms. Given the fact that single-modal antibacterial agent is difficult to drastically eradicate biofilms, the marriage of two kinds of nanozymes is a rational strategy to acquire enhanced performance in combating biofilms. Besides, the utilization of nanozymes circumvents drawbacks of natural enzymes which are costly and vulnerable. Further studies have demonstrated that this kind of artificial enzyme with dual enzyme-mimetic activities can penetrate the biofilms, and inhibit bacterial biofilm formation intensively. Consistently, in vivo anti -biofilm application in treating subcutaneous abscess exhibits commendable wound healing and admirable bactericidal effect . To the best of our knowledge, it is the first time to devise an integrated nanozyme based on the peroxidase-like activity of MOF to eliminate biofilms and kill bacteria on site. This work may promote the application of MOF in the antibacterial field.

研究领域: 生物医学工程 · 微生物学
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SCIENCE OF THE TOTAL ENVIRONMENT · 2022 · IF 10.753

Adenine imprinted beads as a novel selective extracellular DNA extraction method reveals underestimated prevalence of extracellular antibiotic resistance genes in various environments

Qingbin Yuan,Yi Wang,Shangjie Wang,Ruiqing Li,Junlu Ma,Yijing Wang,Ruonan Sun,Yi Luo

Despite severe threats of extracellular antibiotic resistance genes (eARGs) towards public health in various environments, advanced studies have been hindered mainly by ineffective extracellular DNA (exDNA) extraction methods, which is challenged by trace levels of exDNA and inference from abundant coexisting compounds. This study developed a highly selective exDNA extraction method based on molecular imprinting technology (MIT) by using adenine as the template for the first time. Results suggested that adenine imprinted beads were rough spheres at an average size of 0.39 ± 0.07 μm. They effectively adsorbed DNA in the absence of chaotropic agents, with superior capacity (796.2 mg/g), rate (0.0066/s) and regarding DNA of variable lengths, even the ultra-short DNA (<100 bp). They were also highly selective towards DNA, circumventing the interference of competitive compounds' interference. These properties contribute to efficient exDNA extraction (71 %–119 %) from various environmental samples. Specifically, adenine imprinted beads enabled significantly higher extraction rates of eARGs from river, air and vegetable samples (69 %–95 %) compared to that by commercial DNA extraction products (16 %–62 %). The adenine imprinted beads-based method reveals underestimated eARG levels in the environment and the corresponding risks, and thus will thus be a powerful tool for advanced exDNA research.

研究领域: 微生物学 · 环境科学 · 分子生物学
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Journal of Environmental Chemical Engineering · 2023 · IF 7.7

Selective extracellular DNA (exDNA) extraction method reveals underestimated associations between extracellular antibiotic resistance genes and bacteria in diverse environments

Qingbin Yuan,Shangjie Wang,Yuying Chen,Xiaohan Li,Yisi Xu,Ruiqing Li,Yi Wang,Yi Luo

Extracellular antibiotic resistance genes (exARGs) constitute a significant type of antibiotic resistance genes. However, current exARGs studies are restricted due to the lack of efficient extraction methods for extracellular DNA (exDNA), which are laborious, dependent on extra experimental agents, and prone to interference by coexisting substances. In this study, we have developed an ultra-selective exDNA extraction method based on molecular imprinting technology . The resulting guanine imprinted beads are micron grade spheres with high capacity (384.6 mg/g) and speed (90% adsorption in 10 min) for DNA adsorption at variable lengths, including ultra-short DNA (<100 bp), without requiring extra agents. The guanine-imprinted beads demonstrated exclusive DNA adsorption capabilities and avoided interference by other competing substances. Furthermore, guanine imprinted beads effectively extracted DNA at ideal recovery efficiencies (81%∼109%) from diverse environments, such as soil, air, river water and vegetable. Higher abundance of exARGs was obtained by using guanine imprinted beads than currently used commercial magnetic beads. In addition to exDNA extraction quality, a higher diversity of exDNA-releasing bacteria was acquired by guanine imprinted beads. This contributes to 1.2-fold increase in ARG-genera (172 v.s. 150) and 3.6-fold increase in ARG-pathogen associations (96 v.s. 27), indicating a greater number of bacterial hosts of ARGs. This study provides a simple and robust method for advanced exDNA studies, such as discovering novel exARGs and identifying hosts of exARGs.

研究领域: 环境科学 · 微生物学 · 遗传学
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Frontiers in Microbiology · 2022 · IF 6.064

Antibiofilm property and multiple action of peptide PEW300 against Pseudomonas aeruginosa

Wang Meng,Deng Zifeng,Li Yanmei,Xu Keyong,Ma Yi,Yang Shang-Tian,Wang Jufang

Pseudomonas aeruginosa (P. aeruginosa), an opportunistic pathogen, is often associated with difficulties in treating hospital-acquired infections. Biofilms formed by P. aeruginosa significantly improve its resistance to antimicrobial agents, thereby, posing a great challenge to the combat of P. aeruginosa infection. Antimicrobial peptides (AMPs) have recently emerged as promising antibiofilm agents and increasingly attracting the attention of scientists worldwide. However, current knowledge of their antibiofilm behavior is limited and their underlying mechanism remains unclear. In this study, a novel AMP, named PEW300, with three-point mutations (E9H, D17K, and T33A) from Cecropin A was used to investigate its antibiofilm property and antibiofilm pathway against P. aeruginosa. PEW300 displayed strong antibacterial and antibiofilm activity against P. aeruginosa with no significant hemolysis or cytotoxicity to mouse erythrocyte and human embryonic kidney 293 cells. Besides, the antibiofilm pathway results showed that PEW300 preferentially dispersed the mature biofilm, leading to the biofilm-encapsulated bacteria exposure and death. Meanwhile, we also found that the extracellular DNA was a critical target of PEW300 against the mature biofilm of P. aeruginosa. In addition, multiple actions of PEW300 including destroying the cell membrane integrity, inducing high levels of intracellular reactive oxygen species, and interacting with genomic DNA were adopted to exert its antibacterial activity. Moreover, PEW300 could dramatically reduce the virulence of P. aeruginosa. Taken together, PEW300 might be served as a promising antibiofilm candidate to combat P. aeruginosa biofilms.

研究领域: 微生物学 · 分子生物学 · 传染病学 · 药学
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JOURNAL OF HAZARDOUS MATERIALS · 2023 · IF 13.6

Soil minerals and organic matters affect ARGs transformation by changing the morphology of plasmid and bacterial responses

Hongyu Shi,Xinyi Hu,Jin Zhang,Wenxuan Li,Jiang Xu,Baolan Hu,Liping Ma,Liping Lou

Soil environment is a vital place for the occurrence and spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Extracellular DNA-mediated transformation is an important pathway for ARGs horizontal transfer and widely exists in soil environment. However, little information is available on how common soil components affect ARGs transformation. Here, three minerals (quartz, kaolinite , and montmorillonite) and three organic matters (humic acid, biochar, and soot) were selected as typical soil components. A small amount in suspension (0.2 g/L) of most soil components (except for quartz and montmorillonite) promoted transformant production by 1.1–1.6 folds. For a high amount (8 g/L), biochar significantly promoted transformant production to 1.5 times, kaolinite exerted a 30 % inhibitory effect. From the perspective of plasmid, biochar induced a higher proportion of supercoiled plasmid than kaolinite; more dissolved organic matter and metal ions facilitated plasmid aggregation under the near-neutral pH, thus promoted transformation. As for the influence of materials on recipient, although biochar and kaolinite both increased reactive oxygen species (ROS) level and membrane permeability, biochar up-regulated more ROS related genes, resulting in intracellular ROS production and up-regulating the expression of carbohydrate metabolism and transformation related genes. While kaolinite inhibited transformation mainly by causing nutrient deficiency.

CAS / MDL: 1415-93-6
研究领域: 环境科学 · 微生物学 · 土壤学 · 遗传学
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BIOMACROMOLECULES · 2023 · IF 6.2

Degradable Poly(amino acid) Vesicles Modulate DNA-Induced Inflammation after Traumatic Brain Injury

Cong Wei,Peipei Li,Lixin Liu,Hong Zhang,Tianyu Zhao,Yongming Chen

Following brain trauma, secondary injury from molecular and cellular changes causes progressive cerebral tissue damage. Acute/chronic neuroinflammation following traumatic brain injury (TBI) is a key player in the development of secondary injury. Rapidly elevated cell-free DNAs (cfDNAs) due to cell death could lead to production of inflammatory cytokines that aggravate TBI. Herein, we designed poly(amino acid)-based cationic nanoparticles (cNPs) and applied them intravenously in a TBI mice model with the purpose of scavenging cfDNA in the brain and suppressing the acute inflammation. In turn, these cNPs could effectively eliminate endogenous cfDNA, inhibit excessive activation of inflammation, and promote neural functional recovery.

CAS / MDL: 17372-87-1 15086-94-9
研究领域: 神经科学 · 药学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2023 · IF 9.7

Cationic brush hybrid nanoparticles scavenge cell-free DNA to enhance rheumatoid arthritis treatment

Xingliang Liu,Shi Chen,Lixin Liu,Yongming Chen

Abnormally high level of cell-free DNA (cfDNA) is one of the important causes of autoimmune diseases, which aggravate the symptoms of rheumatoid arthritis (RA). Recently, the utilization of cationic polymeric nanoparticles for scavenging cfDNA has emerged as a promising therapeutic strategy for the treatment of RA. However, the intravenous introduction of cationic polymeric nanoparticles into the circulation carries a risk of dissociation, causing toxicity. To realize the potential clinical translation, we employed a series of silica particles grafted with poly(2-(dimethylamino) ethyl methacrylate) (PDMA) (SiNP@PDMA) brush, which possess adjustable PDMA content (100, 200, and 300 degree of polymerization (DP)) and particle size (50, 100, and 200 nm diameter), to selectively scavenge cfDNA in inflamed joint cavity. We demonstrate that the binding affinity for cfDNA, cytotoxicity, circulation time in vivo and retention in the inflamed joint cavity are influenced by the core-shell structure of SiNP@PDMA, ultimately impacting therapeutic efficacy. Among them, SiNP@PDMA with 100 nm size and 200 DP of PDMA exhibit enhanced accumulation and prolonged retention time in inflammatory joint cavity, resulting in superior therapeutic effect. Therefore, in this study, applying the precisely tuning size and cation content of SiNP@PDMA, we demonstrated the factors to matter the therapeutic effect of cationic nanoparticles, which deepened the understanding of the anti-inflammatory therapies based on cfDNA scavenger for RA. Statement of significance Inspired by the discovery that cfDNA would induce inappropriate immune responses to exacerbate the progress of RA, we innovatively employed SiNP@PDMA as a cfDNA scavenger to inhibit cfDNA-induced inflammation in RA. Increase in the cation content efficiently strengthened the binding between SiNP@PDMA and cfDNA, leading to an improvement in inhibitory effect of inflammation. In addition, we compared the behaviors of 50, 100 and 200 nm SiNP@PDMA in RA symptom suppression, local cfDNA scavenging and inflammation inhibition. The results demonstrated that SiNP 100 -PDMA 200 outperformed other analogues, corresponding to their more favorable distribution in inflammatory articular cavity. Together, this study revealed the structure-property relationship of cfDNA scavengers for further development of safe and effective cfDNA scavenging system.

研究领域: 纳米技术 · 风湿病学 · 药学
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BIOMATERIALS · 2021 · IF 12.479

Topical cationic hairy particles targeting cell free DNA in dermis enhance treatment of psoriasis

Yanzi Yan,Huiyi Liang,Xingliang Liu,Lixin Liu,Yongming Chen

Abnormal high level of cell free DNA (cfDNA) triggers chronic inflammation to exacerbate psoriasis symptoms. Scavenging cfDNA by topical cationic polymeric nanoparticles has been certified as an effective therapeutic strategy for treating psoriasis. However, cationic cfDNA scavengers have a great potential risk to organs after entering systemic circulation through skin barrier. For better transformation to clinical application, herein a series of poly(2-(dimethylamino)ethyl methacrylate) (PDMA) grafted hairy silica particles (cSPs) with tunable PDMA length and particle size are applied to scavenge cfDNA in dermis. We reveal that the structure of cSPs correlates with the permeation ability across stratum corneum, retention time in dermis, binding affinity to cfDNA, and toxicity tolerance, which in turn affect the therapeutic effect. Especially, the cSPs of 700 nm show more accumulation and longer retention in psoriatic lesions, leading to excellent treatment results. They also outperform the cSPs of 200 nm at a lower administration frequency. Thus, we address the issues of size, cationic content of cSPs to open a potential new avenue to topically treatment of psoriasis by targeting cfDNA in dermis.

研究领域: 药学 · 纳米技术 · 皮肤科 · 材料科学
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ADVANCED FUNCTIONAL MATERIALS · 2020 ·Vol. 30 ·期 27 ·2000391 · IF 16.836

Cationic Block Copolymer Nanoparticles with Tunable DNA Affinity for Treating Rheumatoid Arthritis

Jingjiao Wu,Huiyi Liang,Yuanchao Li,Yi Shi,Massimo Bottini,Yongming Chen,Lixin Liu

A high concentration of cell-free DNA (cfDNA) in joints is considered a disease causative agent of rheumatoid arthritis (RA) and cfDNA scavenging has been regarded as an efficient therapeutic avenue. Cationic polymers can hamper progression of joint inflammation in a rat model of RA by scavenging cfDNA; however, they may cause systemic toxicity due to the strong positive charges. To reduce the toxicity, herein a library of cationic nanoparticles (cNPs) of block copolymer micelles is developed and the effects of structure and surface composition on cNP efficacy to bind nucleic acids, toxicity, and therapeutic activity on a collagen induced arthritis (CIA) rat model of RA are assessed. The library includes cNPs with a homoshell from poly(lactic- co -glycolic acid)- block -poly(2-(dimethylamino)ethyl methacrylate) (PLGA- b -PDMA) block copolymers and cNPs with a mixed shell of poly(ethylene glycol) (PEG) and PDMA by coself-assembling PLGA- b -PDMA and PLGA- b -PEG block copolymers. Relatively to the homoshell cNPs, introduction of PEG segments translates into a lower DNA binding efficacy while preserving ability to hamper joint inflammation. Moreover, they show a greater accumulation and longer retention at the inflamed joints, allowing a lower administration frequency. In conclusion, this work shows that the therapeutic index of cationic materials can be tuned by introducing surface neutral moieties.

研究领域: 纳米技术 · 生物材料 · 药学 · 风湿病学 · 生物医学工程
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2023 · IF 6.1

Ultraefficient OG-Mediated Photodynamic Inactivation Mechanism for Ablation of Bacteria and Biofilms in Water Augmented by Potassium Iodide under Blue Light Irradiation

Yu-gang Shi,Wen-xuan Chen,Mei-zhi Zheng,Yue-xin Zhao,Yi-ran Wang,Yen-Ho Chu,Shao-ting Du,Ze-yu Shi,Qing Gu,Jian-she Chen

While photodynamic inactivation (PDI) has emerged as a novel sterilization strategy for drinking water treatment that recently attracted tremendous attention, its efficiency needs to be further improved. In this study, we aimed to clarify the ultraefficient mechanism by which potassium iodide (KI) potentiates octyl gallate (OG)-mediated PDI against bacteria and biofilms in water. When OG (0.15 mM) and bacteria were exposed to blue light (BL, 420 nm, 210 mW/cm2), complete sterilization (>7.5 Log cfu/mL of killing) was achieved by the addition of KI (250 mM) within only 5 min (63.9 J/cm2). In addition, at lower doses of OG (0.1 mM) with KI (100 mM), the biofilm was completely eradicated within 10 min (127.8 J/cm2). The KI-potentiated mechanism involves in situ rapid photogeneration of a multitude of reactive oxygen species, especially hydroxyl radicals (•OH), reactive iodine species, and new photocytocidal substances (quinone) by multiple photochemical pathways, which led to the destruction of cell membranes and membrane proteins, the cleavage of genomic DNA and extracellular DNA within biofilms, and the degradation of QS signaling molecules. This multitarget synergistic strategy provided new insights into the development of an environmentally friendly, safe, and ultraefficient photodynamic drinking water sterilization technology.

研究领域: 环境科学 · 水处理 · 微生物学 · 光化学
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