Small
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2025
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IF 12.1
Wei Guan,Xiangmei Liu,Shengli Zhu,Zhaoyang Li,Hui Jiang,Zhenduo Cui,Yufeng Zheng,Shuilin Wu
The global rise in infectious diseases and antibiotic overuse exacerbate bacterial drug resistance, particularly in multidrug-resistant pathogens like methicillin-resistant Staphylococcus aureus (MRSA). While plant-derived flavones exhibit multi-target antibacterial mechanisms that overcome resistance, their therapeutic application remains constrained by poor aqueous dispersibility and stability. Herein, a luteolin-iron complex (Lut-Fe 3 ⁺) is engineered through a facile coordination approach, where Fe 3 ⁺ facilitates d -orbital splitting and generation of high-spin electrons. This octahedral complex demonstrates exceptional water dispersibility and exhibits broad-spectrum absorption across ultraviolet to microwave (MW) frequencies. Lut-Fe 3 ⁺ demonstrates dual antimicrobial modalities: long-term antisepsis in the dark and rapid sterilization under light/MW irradiation. This multi-functional complex is further combined with various methods to develop therapeutic strategies for bacterial infections at different depths. Notably, the Lut-Fe 3 ⁺ is engineered into an MW-responsive nebulization system, achieving effective eradication of MRSA-induced deep-tissue pneumonia in mice.
研究领域:
药理学
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材料科学
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感染性疾病研究
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Yingxin Zhu,Xianzhu Luo,Zihang Yu,Shihui Wen,Guochen Bao,Le Zhang,Cuiling Zhang,Yuezhong Xian
Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for causing life-threatening infections that result in high morbidity and mortality rates. The development of advanced imaging and therapeutic methods for in vivo diagnosis and treatment of MRSA infections remains challenging. Here, we develop a hybrid nanoplatform based on rare-earth-doped nanoparticles (RENPs) sensitized by a moiety-engineered near-infrared (NIR) TPEO-820 dye and with a ZIF-8 layer that incorporates CysNO, a photochemically triggered nitric oxide donor. We then use the hybrid for both NIR-II bioimaging and photoactivatable treatment of MRSA-infected wounds. We show that the NIR dye sensitization leads to an 8.5-fold enhancement of the downshifting emission and facilitates deep-tissue NIR-II imaging of bacterial infections. Moreover, the sensitization strategy enhances the UV emission of RENPs by two orders of magnitude, leading to the efficiently controllable release of nitric oxide for effective disinfection of MRSA in vitro and in vivo. The hybrid nanoplatform thus offers promising opportunities for simultaneous localization and controllable treatment of MRSA. Statement of Significance Early detection and treatment of MRSA infections are crucial for reducing public health risks. It is a significant challenge that develops sensitive in vivo diagnosis and complete elimination of drug-resistant bacterial infections. Herein, a nanoplatform has been developed for photoactivatable therapy of MRSA infections and deep tissue NIR-II imaging. This platform utilizes lanthanide-doped rare earth nanoparticles (RENPs) that are sensitized by a moiety-engineered near-infrared (NIR) dye TPEO-820. The TPEO-820 sensitized RENPs exhibit 5 times increase in the release of NO concentration for MRSA treatment compared to unsensitized RENPs, enabling precise therapy of MRSA infection both in vitro and in vivo. Moreover, the platform demonstrates NIR-II luminescence in vivo, allowing for sensitive imaging in deep tissue for MRSA infection.
研究领域:
生物医学工程
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感染性疾病
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纳米医学
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DOI
PubMed
高影响因子
Arabian Journal of Chemistry
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2023
·
IF 6
Yujie Xu,Xiaoli Zhang,Shuyi Liang,Congmin Niu,Jiayi Guo,Chunbo Lu
There is a serious threat to public health posed by the rapid spread of methicillin-resistant Staphylococcus aureus (MRSA). Photodynamic sterilization is the most effective method of combating bacterial infection, especially multidrug-resistant bacterial infection. In this study, zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, one of the most attractive metal–organic framework material, were used to encapsulate the indocyanine green (ICG, a potent PS); after that, hyaluronic acid (HA) coating was applied to the nanoparticle to create a host cell-tracking nanoplatform (ICG@ZIF-8/HA). Upon near-infrared light irradiation, ICG@ZIF-8/HA exhibit excellent efficacy in producing reactive oxygen species (ROS) and killing multidrug-resistant bacteria in vitro . After the tail vein injection, ICG@ZIF-8/HA can precisely deliver to lung infection sites, and display an effective PDT-based elimination of multidrug-resistant bacteria in mouse lung infection models. These results suggest that the ICG@ZIF-8/HA nanoplatform may exhibit potent curative effects on infectious diseases.
研究领域:
医学
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生物材料学
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感染病学
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DOI
高影响因子
Virulence
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2025
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IF 5.4
Jian-Guo Li,Wei-Cheng Zhong,Long-Gen Zhong,Chao-Yan Niu,Ting-Yin Lu,Chuan-Jian Zhang,Jian Sun,Xiao-Ping Liao,Yu-Feng Zhou
Methicillin-resistant Staphylococcus aureus (MRSA) remains a major therapeutic challenge and poses a significant global health threat. Developing adjuvants to enhance the efficacy of existing antibiotics represents a promising strategy to address this issue. In this study, we evaluated auranofin as an adjuvant to potentiate the activity of linezolid against MRSA. Auranofin significantly increased MRSA susceptibility to linezolid, promoted intracellular linezolid accumulation, and suppressed the emergence of MRSA resistance to linezolid. Mechanistically, auranofin inhibited the Trx/TrxR system, inducing redox imbalance and reactive oxygen species (ROS) accumulation, which triggers DNA damage and transcriptional dysregulation. Auranofin synergized with linezolid to achieve dual inhibition of MRSA protein synthesis. Furthermore, auranofin downregulated the global regulator sarA, impaired SarA DNA-binding activity, and enhanced SarA phosphorylation, thereby attenuating SarA-mediated virulence factors (eg, adhesins and toxins) and biofilm formation. Importantly, auranofin fully restored anti-MRSA activity of linezolid in both Galleria mellonella and murine bacteremia models. Collectively, these findings identify auranofin as a promising adjuvant to linezolid and highlight its potential to improve therapeutic outcomes against invasive MRSA infections.
研究领域:
微生物学
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传染病学
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抗生素耐药性
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药理学
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分子生物学
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PubMed
高影响因子
DRUG DELIVERY
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2026
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IF 8
Haonan Li,Binghong Xu,Junguang Liang,Tao Hu,Tingting Wu,Liqin Lai,Xuan Zou,Ziquan Lv,Xiangjie Yao,Xiaobao Jin,Yinghua Xu,Shuiqing Gui,Xuemei Lu
Current clinical strategies for Methicillin-resistant Staphylococcus aureus (MRSA)-induced acute lung injury (ALI) predominantly focus on single-approach interventions such as anti-inflammatory therapy. However, due to the complex, multi-pathway pathological network underlying the disease, targeting a single pathway often yields suboptimal therapeutic outcomes. Consequently, there is a pressing need to develop innovative drug delivery systems capable of systematically addressing this intricate pathological process. Geraniol, a naturally derived monoterpene alcohol, exhibits multiple pharmacological activities including antimicrobial, antioxidant, and organ-protective effects, while the antimicrobial peptide (AMP) FK13-a1 demonstrates broad-spectrum antibacterial, anti-inflammatory, and immunomodulatory functions. Recognizing their complementary mechanisms of action, we innovatively propose a synergistic therapeutic strategy combining geraniol with FK13-a1. To enhance targeting precision, we engineered a biomimetic delivery system by coating nanomaterials with macrophage membranes via tyramine linkage, enabling specific homing to pulmonary inflammatory sites. Guided by this design concept, we successfully fabricated the biomimetic nanodrug Tyr-MM@PLGA/G+F and conducted systematic characterization using multiple analytical techniques. Through established in vitro and in vivo infection models, we evaluated the therapeutic efficacy of this nanosystem. Results demonstrated that Tyr-MM@PLGA/G+F actively targets ALI lesion sites, achieving precise co-delivery and synergistic action of geraniol and FK13-a1 at the pathological foci, thereby significantly enhancing treatment outcomes. This study not only validates the remarkable efficacy of this composite nanosystem against ALI but also provides novel insights and experimental evidence for targeted therapy of this condition.
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PubMed
高影响因子
Advanced Science
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2026
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IF 14.1
Qiang Shi,Renliang Zhao,Jia Wang,Zhenchen Xiong,Xiangtian Deng,Cheng Zheng,Wenzhi Zhang
MRSA infections give rise to chronic cutaneous and advance into profound tissue invasions, including osteomyelitis and sepsis—conditions for which existing clinical interventions offer only limited efficacy. The utility of broad-spectrum antibiotics has become increasingly compromised by escalating drug resistance, inadequate tissue targeting, and deleterious side effects. Neutrophil extracellular traps (NETs) have emerged as a compelling immunotherapeutic avenue for eradicating multidrug-resistant pathogens. Inspired by the bactericidal and immunoregulatory functions of NETs, we developed a photothermal–immunomodulatory hydrogel reinforced by a Ti 3 C 2 /ZnAl-LDH nanoplatform to mimic NETs-like antimicrobial defense while overcoming their inherent limitations. Hollow photothermal nanoparticles were fabricated from 2D Ti 3 C 2 and ZnAl-LDH (TiZ) nanosheets and infused with chlorogenic acid, forming CTiZ. These were cloaked in membranes derived from apoptotic neutrophils to create a NETs-mimetic functional bacterial trapper (CTiZM), which was then encapsulated within a thermoresponsive dopa-poly(N-isopropylacrylamide) hydrogel (dopa-PNIPAm, DP), yielding a composite hydrogel system designated CTiZM@DP. This sophisticated platform amplifies antibacterial potency through effective microbial entrapment and the generation of reactive oxygen species, while simultaneously orchestrating the polarization of macrophages toward a reparative M2 phenotype under the influence of gentle photothermal stimulation. Collectively, this integrative strategy heralds a promising therapeutic modality for the eradication of multidrug-resistant infections and the enhancement of wound healing in individuals with diabetes.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Guannan Le,Xiaoyu Ma,Ling Cai,Wei Wei,Jinhuan Li,Jin Chen
The effectiveness of antibiotic treatment for bacterial-infected wounds has been greatly hampered by the increasing antimicrobial resistance (AMR) caused by improper antibiotic use. It is thereby demanding for the deployment of antibiotic-free and on-demand therapeutic strategies, such as chemodynamic therapy (CDT) and photothermal therapy (PTT). Here, via a desolvation method, L ysozyme- H emin nanocomposite was firstly prepared and further decorated by S ilver nanoparticles to form LHS NPs, which was then incorporated into a thermosensitive hydrogel. The LHS NPs demonstrated remarkable peroxidase-like activity and photothermal effect, with a specific activity of 2.59 U/mg and a photothermal conversion efficiency of 53.89 %. Consequently, it was found that the formed LHS NPs exhibited superior antibacterial activity against both Gram-negative and Gram-positive bacteria without the using of antibiotics. Moreover, through the optimization of nanozymes and hydrogels, the obtained nanozyme-hydrogel composite could adhere to wound sites of various shapes within 2 min upon NIR irradiation, enabling the on-demand wound treatment. Notably, in a methicillin-resistant Staphylococcus aureus ( MRSA )-infected wound model, the nanocomposite demonstrated excellent antibacterial activity and greatly sped up wound healing. Therefore, the LHS nanoparticles-loaded thermosensitive hydrogel as an integrated CDT/PTT therapeutic nanoplatform holds enormous potential in combating drug-resistant bacteria towards the complex infected wounds management.
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PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 10
·1458
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IF 4.8
Xin Meng,Zhiyun Yu,Chao Ning,Mingtong Sun,Mengna Kang,Haiyong Guo
Background:The treatment of methicillin-resistantStaphylococcus aureus(MRSA) infections is extremely challenging due to its antibiotic resistance, and the combination of plant active ingredients with antibiotics represents a potential strategy to address this issue.Methods:We determined the combinatorial relationship between baicalin (BA) and kanamycin (KM) using the checkerboard dilution method. The antibacterial activity of the baicalin–kanamycin (BA/KM) combination was evaluated through growth curve determination assays and scanning electron microscopy (SEM). The effects of the BA/KM combination on the cell membrane and cell wall of MRSA were analyzed using reactive oxygen species (ROS) detection assays, intracellular protein leakage experiments, alkaline phosphatase (AKP) activity assays, laser scanning confocal microscopy (LSCM) observations, and molecular docking simulations. The antibiofilm activity and related mechanisms of the BA/KM combination were elucidated via crystal violet staining, MTT assay, phenol-sulfuric acid method, congo red staining, staphyloxanthin determination assays, and quantitative real-time polymerase chain reaction (qPCR). The safety of the BA/KM combination was assessed through hemolytic activity analysis, and its anti-MRSA efficacy was evaluated on lettuce.Results:BA/KM combination showed a synergistic antibacterial effect on MRSA USA300. Mechanistic studies revealed that BA may interact with amino acid residues of peptidoglycan synthetase PBP2a to hinder peptidoglycan synthesis, thereby facilitating KM penetration through the cell wall. Subsequently, BA binds to amino acid residues of the membrane transporter NorA, leading to disruption of cell membrane homeostasis and enhancing KM’s ability to induce intracellular ROS accumulation in MRSA. Furthermore, the BA/KM combination reduced MRSA biofilm formation by 77.85% and decreased the metabolic activity of biofilm cells by 42.93% through inhibiting the synthesis of biofilm components EPS and PIA. Additionally, this combination suppressed the synthesis of staphyloxanthin and downregulated the expression ofagrAandagrCgenes. When 1/8 MIC BA was combined with 1/4 MIC KM, the count of MRSA on lettuce surfaces was reduced by 0.88 log CFU/cm2, an effect comparable to that of 0.2% (v/v) hydrogen peroxide.Conclusions:According to these findings, the BA/KM combination may offer a promising option for enhancing antibacterial efficacy through synergism, reducing antibiotic usage concentrations, and limiting MRSA transmission in fresh agricultural products.
研究领域:
微生物学
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药理学
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分子生物学
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植物天然产物
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抗生素联合疗法
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食品安全
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DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
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IF 10.7
Lihua Li,Li Ren,Qiuhan Zhao,Ke Xu,Qiushuang Wu,Qianru Su,Xin Li,Xin Lü,Li Wang
The management of wounds infected with drug-resistant bacteria represents a significant challenge to public health globally. Nanotechnology-functionalized photothermal hydrogel with good thermal stability, biocompatibility and tissue adhesion exhibits great potential in treating these infected wounds. Herein, a novel photothermal hydrogel (mCS-Cu-Ser 1 ) was prepared through in situ mineralization in the hydrogel networks and ion cross-linking driven by copper ions (∼3 mM). Self-assembling polyphosphate sericin nanoparticles (Ser NPs) formed by an ultrasound-assisted anti-solvent method were as mineralization templates and gallic acid-grafted chitosan (mCS) was prepared as the sole matrix. Grafting of polyphenols and cross-linking of copper ions endowed mCS-Cu-Ser 1 with injectable, skin-adhesive and self-healing characteristics. Due to the nonradiative relaxation of Cu 2+ electron-hole pairs of copper phosphate on the surface of Ser NPs and the molecular thermo-vibrational effect of the mCS-Cu complex, mCS-Cu-Ser 1 rapidly warmed up to 50 °C within one minute under near-infrared (NIR) irradiation. Integrating such excellent photothermal properties with antimicrobial activity and intracellular reactive oxygen species scavenging from mCS, mCS-Cu-Ser 1 + NIR effectively accelerated methicillin-resistant Staphylococcus aureus (MRSA) infected wound healing. This work develops a novel dressing for the treatment of MRSA-infected wounds and provides some reference for the preparation of multifunctional acid-free chitosan hydrogels.
研究领域:
生物医学工程
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材料科学
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微生物学
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DOI
PubMed
高影响因子
Food Chemistry-X
·
2024
·
IF 6.5
Fei Zeng,Shijuan Shao,Zhilu Zou,Siqi Guo,Yu Cai,Chunchao Yan,Yunzhong Chen,Maolin Wang,Tingting Shi
Licorice flavonoids (LFs) exhibit potent antibacterial activities against Gram-positive bacteria. However, the related mechanism remains unclear. This study aims to illustrate the mechanisms of licochalcone A (LA), a main flavonoid in LFs, against methicillin-resistant Staphylococcus aureus (MRSA). The anti-MRSA effect of LA was comprehensively investigated by a combination of proteomics and metabolomics studies. Meanwhile, LA was loaded in glycyrrhizin (GA) micelles (GA@LA micelles) to improve its water solubility. The results demonstrated that LA could disrupt the arginine metabolism and cause the accumulation of intracellular ROS in MRSA. In addition, LA could inhibit the expression of glucokinase in MRSA, which affect the synthesis of ATP, fatty acids, and peptidoglycan. GA@LA micelles have the latent ability to inhibit the growth of MRSA on fresh pork.
研究领域:
微生物学
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药理学
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食品科学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
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IF 10.317
Zihan Mei,Duyang Gao,Dehong Hu,Huichao Zhou,Teng Ma,Liang Huang,Xin Liu,Rongqin Zheng,Hairong Zheng,Ping Zhao,Jianqiao Zhou,Zonghai Sheng
Multidrug-resistant Staphylococcus aureus (MRSA) seriously endanger human health. The development of efficient methods to eliminate the infections and monitor the treatment process are of great significance. Near-infrared-II (NIR-II) photoacoustic (PA) imaging and photothermal therapy (PTT) are highly integrated theranostic platforms with superior performance including a low imaging background, increased tissue penetration depth, and high photothermal threshold. Herein, we report an activatable near-infrared II (NIR-II) phototheranostic strategy using miniature Au/Ag nanorods (NRs) for the photochemical synergistic therapy of MRSA infections and in situ monitoring of the treatment progress. Au/Ag NRs were efficiently activated by ferricyanide solution and allowed to continuously release free Ag + to eliminate MRSA, triggering NIR-II photothermal and PA performance enhancement. The activated NIR-II photothermal effect in turn accelerated the release of free Ag + from Au/Ag NRs for the synergistic elimination of gram-positive Staphylococcus aureus and promoted wound healing. No photothermal damages or free Ag + -induced side effects were observed in treated mice. After synergistic treatment, a 20-fold NIR-II PA signal increase with a maximum signal-to-noise measurement of 9.5 was observed between the implanted site and normal tissue, enabling sensitive monitoring of Ag + release process. The prepared Au/Ag NRs were stable and biocompatible, showing great potential for activatable NIR-II phototheranostic application.
研究领域:
生物医学工程
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纳米医学
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感染性疾病研究
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Zhiwen Ge,Xiaohong Chen,Renqin Yang,Wei Li,Baixing Yin,Zhiyu Li,Mingsheng Dong
In this work, we reported an in situ exopolysaccharide ( in situ -EPS1) containing rare fucose produced by Lactobacillus helveticus MB2-1 in Sayram ketteki yoghurt, which made it unique. Its fine structure was characterized by GPC, HPLC, FT-IR, GC–MS, 1 HNMR and 13 CNMR together with two-dimensional (2D) NMR spectra. The results revealed that in situ -EPS1 was a new heteropolysaccharide with molecular weight of 1.06 × 10 5 Da, and was composed of mannose, rhamnose, glucose, galactose and fucose with the following repeating units. Download : Download high-res image (31KB) Download : Download full-size image Furthermore, the in situ -EPS1 exhibited significant antibiofilm effect against Methicillin-resistant Staphylococcus aureus (MRSA). Notably, the in situ -EPS1 did not interfere with the planktonic growth of MRSA strain, whereas inhibited its cell metabolic activity and the transcription of genes related to biofilm formation. This unique antibiofilm but non-antibacterial mechanism supposedly prevented the development of bacterial drug resistance, which may open a new door to fight against these drug-resistant microorganisms.
研究领域:
微生物学
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食品科学
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生物化学
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药学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）