Journal of Global Antimicrobial Resistance
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2016
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IF 1.087
Dongmei Wu,Ruochen Lu,Yuquan Chen,Jie Qiu,Chaocheng Deng,Qiang Tan
This study aimed to determine whether selection by antibiotics, chlorhexidine (CHX) and Rhizoma coptidis extract (RCE) would lead to cross-resistance or decreased susceptibility in Staphylococcus aureus . The S. aureus reference strain ATCC 25923 as well as 14 clinical isolates were exposed to antibiotics, CHX and RCE at sublethal doses for up to 14 days. Changes in susceptibility were determined by analysis of minimum inhibitory concentrations (MICs). All isolates were cross-resistant to more than one other antibiotic following tetracycline exposure, and increased resistance (≥4-fold MIC increase) to RCE and CHX was observed in six and three isolates, respectively. Following selection by CHX, most of the treated strains showed no significant change in sensitivity to CHX. However, all strains developed cross-resistance to at least one antibiotic, and decreased susceptibility (≥4-fold MIC increase) to RCE appeared in seven strains. Following exposure to RCE, 11 isolates showed cross-resistance to at least one antibiotic. In addition, three RCE-exposed strains showed reduced susceptibility to CHX (4- or 8-fold MIC increase). The results obtained in this study imply that antibiotics, biocides and antimicrobial Chinese herbs might employ some of the same mechanisms of action against bacteria, triggering mutual cross-resistance to further foster the development of bacterial resistance.
研究领域:
微生物学
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感染病学
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药理学
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分子生物学
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抗菌药物耐药性
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天然药物学
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DOI
高影响因子
ELECTROCHIMICA ACTA
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2026
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IF 5.8
Tiance Gu,Qingqing Wu,Dongying Liu,Xueran Shi,Binfang Yuan,Beibei Liang,Jing Wang,Qian Han
Porous porphyrin hydrogel (SCT hydrogel) showed stable ECL performance via spatial-confined effect. • The interface effect between CNTs and the SCT hydrogel led to the ECL enhancement. • A label-free ECL immunosensor was constructed for S. aureus detection based on CNTs and SCT hydrogel. • This ECL immunosensor enabled rapid and ultrasensitive detection of S. aureus in milk, water, and pork samples. Functionalized hydrogel-based electrochemiluminescence (ECL) devices still face the challenges of insufficient luminescence efficiency and sensing interface modification. Herein, we propose the carbon nanotubes (CNTs)-boosted porphyrin hydrogel ECL sensing strategy. The three-dimensional porous porphyrin hydrogels (SCT hydrogels) are composed of a dual-crosslinked sodium alginate (SA) and chitosan (CS) network encapsulating a water-soluble ECL luminophore (5,10,15,20-tetrakis (4-sulfonatophenyl) porphyrin, TPPS). The spatial-confinement effect significantly enhanced the ECL stability of TPPS, as confirmed by finite element analysis. Furthermore, four types of CNTs are separately employed as sensing scaffolds to reduce the electrical resistance of hydrogel. Notably, carboxylated CNTs provide greater ECL enhancement than non-carboxylated ones, with carboxylated multi-walled CNTs (MWCNTs-COOH) yielding the best improvement (1.87-fold that of the SCT hydrogel alone). Interestingly, the interface effect between CNTs and SCT hydrogel contributes to a higher ECL enhancement than their mutual doping. Electrochemical techniques, ECL methods, and density functional theory systematically reveal the improvement mechanism of CNTs. Furthermore, the MWCNTs-COOH-assisted SCT hydrogel is used to construct a label-free and highly sensitive ECL immunosensor for Staphylococcus aureus detection. By establishing CNTs as a pivotal promoter, this work opens the potential of flexible hydrogel-based ECL sensors for rapid and sensitive foodborne pathogen detection. A label-free ECL immunosensor for Staphylococcus aureus achieves outstanding performance, driven by the spatial-confined effect of a porous porphyrin hydrogel and the interface effect between CNTs and the SCT hydrogel. Download: Download high-res image (360KB) Download: Download full-size image
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PLoS Pathogens
·
2026
·Vol. 22
·期 9
·e1014644
·
IF 4.9
Yunfei Wei,Xinyu Zhao,Ziyi Yin,Yanmin Zhang,Yaxin Zhai,Baihe Zhan,Yeling Wang,Jiakang He,Jianfeng Wang,Xuming Deng,Lei Xu,Haihua Feng
Staphylococcus aureus ( S. aureus ), a major pathogen of mastitis, employs a diverse arsenal of virulence factors to invade and disrupt mammary tissues, thereby eliciting a complex and dysregulated inflammatory response. Sphingomyelin phosphodiesterase (Sph) has emerged as a key virulence determinant of S. aureus ; however, its potential role and underlying mechanisms in mastitis remain elusive. In this study, we demonstrate that Sph deficiency significantly suppresses S. aureus -induced ferroptosis. Mechanistically, Sph disrupts mitochondrial cristae through interaction with Mic60, a core component of the mitochondrial contact site and cristae-organizing system (MICOS). Sph-mediated cytosolic mitochondrial DNA (mtDNA) released is sensed by cyclic GMP-AMP synthase (cGAS), leading to activation of the STING signaling pathway, which further triggers the recruitment of GPX4 into the autophagy-lysosome pathway for degradation. Collectively, our study unveils a novel pathogenic mechanism whereby the S. aureus virulence factor Sph perturbs mitochondrial homeostasis, and engages the cGAS-STING axis to promote GPX4 degradation and ferroptosis, highlighting Sph as a potential therapeutic target for S. aureus -associated mastitis.
S. aureus is a major etiological agent of mastitis, a prevalent inflammatory disease of the mammary gland that adversely affects animal health and milk production. During infection, S. aureus deploys a diverse repertoire of virulence factors to damage host cells and promote disease progression. Among these factors, sphingomyelin phosphodiesterase (Sph) has been implicated in host cell injury; however, its contribution to mastitis pathogenesis remains poorly understood. Here, we show that Sph perturbs mitochondrial homeostasis by interacting with Mic60 and disrupting mitochondrial cristae architecture, thereby triggering activation of the cGAS-STING signaling pathway. Activated STING subsequently promotes the autophagic degradation of GPX4, a key antioxidant enzyme that protects cells against lipid peroxidation, ultimately driving ferroptotic cell death. Collectively, our findings uncover a previously unrecognized mechanism, and identify Sph as a potential therapeutic target for S. aureus -associated mastitis.
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PubMed
高影响因子
Virulence
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2026
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IF 6.8
Zheng-Jie Xue,Ming-Yu Huang,Jun-Feng Wang,Si-Yi Zhong,Zheng-Cheng Yang,Jian Xu,Bo Jin,Ni-Pi Chen,Chao-Dong Qian
Staphylococcus aureus small colony variants (SCVs) pose a clinical challenge due to antibiotic tolerance and recurrent infections. Targeting the bacterial respiratory chain offers a potential strategy to overcome SCV-mediated resistance. Here we show that cryptotanshinone (CT) selectively inhibits S. aureus’s NDH-2 isoform NdhC. Antimicrobial assays showed that ndhC overexpression doubled bacterial sensitivity to CT, while ndhF overexpression had no effect. In vitro enzymatic analysis indicated that CT inhibits NdhC, with noncompetitive inhibition against NADH and uncompetitive inhibition against menadione (MD). Molecular docking and site-directed mutagenesis identified threonine T352 as critical for CT binding to the NdhC-MD complex. Using membrane vesicle assays and cellular thermal shift assays, we obtained evidence that CT acts at NdhC in isolated membrane preparations in a substrate-dependent manner. Notably, gentamicin-induced SCVs carrying fusA and perR mutations exhibited collateral sensitivity to NDH-2 inhibitors. Further characterization of menaquinone (MK) auxotrophic SCVs, which harbor a frameshift mutation in menC and show reduced but detectable NADH dehydrogenase activity, revealed that these variants also display heightened susceptibility to CT, consistent with the notion that residual NdhC activity in respiratory-compromised cells remains targetable. Together, these findings provide insights into the molecular targeting of NdhC by CT and support the concept that the metabolic vulnerability of SCVs may be exploitable for the treatment of refractory S. aureus infections.
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PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2026
·Vol. 40
·期 7
·e70982
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IF 3.6
Zimeng Liu,Yunpeng Gao,Musen Li,Qingsong Sun,Yunhe Fu,Yue Zhang
Mastitis is a prevalent gynecological disorder in women, with Staphylococcus aureus ( S. aureus ) serving as a primary etiological pathogen of this condition. Cryptotanshinone (CPT) has been demonstrated to exert anti-oxidative stress and anti-inflammatory effects, conferring therapeutic benefits for a diverse range of inflammatory diseases. However, its efficacy and underlying regulatory mechanisms in ameliorating S. aureus -induced mastitis remain elusive. Therefore, the present study was designed to elucidate the protective effects and molecular regulatory mechanisms of CPT against S. aureus -induced mastitis. A murine model of S. aureus -induced mastitis was established via intramammary injection of S. aureus , and CPT was administered to the model mice for therapeutic intervention. In vivo experiments revealed that CPT administration mitigated S. aureus -induced mastitis in mice by suppressing the production of pro-inflammatory cytokines and inhibiting ferroptosis. In vitro, CPT abrogated the S. aureus -induced elevation of TNF-α, IL-1β, MDA, ROS, and Fe 2+ levels in mouse mammary epithelial cells (MMECs); additionally, it restored the ATP and GSH levels that were reduced by S. aureus stimulation in these cells. Furthermore, CPT concentration-dependently upregulated the expression of GPX4, Nrf2 and HO-1 in MMECs. Notably, the inhibitory effects of CPT on S. aureus -induced inflammatory responses and ferroptosis were abrogated in Nrf2-knockdown MMECs. In conclusion, this study demonstrates that CPT exerts a robust protective effect against S. aureus -induced mastitis by suppressing inflammatory responses and inhibiting ferroptosis through the activation of the Nrf2/GPX4 signaling pathway.
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DOI
PubMed
高影响因子
Biosensors-Basel
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2026
·Vol. 16
·期 8
·415
·
IF 6.2
Zuoping Lv,Xiaoru Tan,Peilong Chen,Mingshuo Qu,Weijin Guo,Jihong Huang,Xin Cui
Foodborne infections and enterotoxin poisoning caused byS. aureuspose serious threats to food safety and public health. However, conventional detection methods are often time-consuming, technically complex, and typically require relatively large sample volumes. Herein, we report an aptamer-functionalized rough gold nanoparticle (RPG)-based photothermal platform that enables rapid and quantitative detection ofS. aureususing a smartphone-compatible thermal imaging system in combination with a laser and an infrared thermal camera. RPGs were synthesized via a facile one-step method, and exhibited uniform particle size and a measured photothermal conversion efficiency of ~73.20%. After optimization of the aptamer concentration, laser irradiation time, and probe concentration, the proposed method exhibited a wide detection range from 1.0 × 102to 1.0 × 107cfu/mL, with an operational detection threshold of 100 CFU/mL under the optimized experimental conditions, a total assay time of less than 40 min, and a sample requirement of only 30 μL per assay, while maintaining acceptable reproducibility. Spike-and-recovery experiments in real samples, including orange juice, tap water, and milk, yielded recoveries of 91.8–105.5%, indicating suitable analytical performance in complex matrices. This work provides a rapid, portable, and low-sample-volume detection strategy forS. aureus, offering a practical approach for on-site food safety monitoring.
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高影响因子
Biomaterials Research
·
2025
·
IF 9.6
Sidi Zheng,Xinshu Zou,Yanru Wei,Xilong Cui,Shuang Cai,Xiubo Li,Zhiyun Zhang,Yanhua Li
The ever-increasing emergence and prevalence of multidrug-resistant bacteria accelerate the desire for the development of new antibacterial strategies. Although antibacterial phytochemicals are a promising approach for long-term treatment of resistant bacteria, their low antibacterial activity and poor solubility hinder their practical applications. Here, the natural antibacterial compound sanguinarine (SG) together with gallic acid–ferrous coordination nanoparticles (GA-Fe(II) NPs) was encapsulated in a near-infrared (NIR)-activated thermo-responsive liposome. By virtue of the photothermal effect of GA-Fe(II) NPs, the nanoplatform released SG on demand upon NIR irradiation. Additionally, the heat can boost the Fenton reaction triggered by GA-Fe(II) NPs to generate hydroxyl radicals and perform sterilization. By coupling with photothermal therapy, chemodynamic therapy, and SG-based pharmacotherapy, the platform showed enhanced antibacterial efficiency and an antibiofilm effect toward methicillin-resistant Staphylococcus aureus and reduced the risk of developing new bacterial resistance. This antibacterial system displayed excellent antibacterial activity in a methicillin-resistant S. aureus-caused skin abscess, demonstrating its potential clinical application. Moreover, transcription analysis clarified that the platform achieved a synergistic antibacterial effect by attacking the cell membrane, inducing energy metabolism disorder, inhibiting nucleic acid synthesis, etc. The developed NIR-controlled phytochemical-loaded platform offers new possibilities for killing antibiotic-resistant bacteria and avoiding bacterial resistance, making it contributory in the fields of anti-infective therapy and precision medicine.
研究领域:
药学
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微生物学
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纳米医学
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DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
·
IF 10
Hailin Xie,Yuna Qian,Jiayi Ding,Rui Zhao,Linwei Huang,Jianliang Shen,Zhihua Zhou
The treatment of infected pressure ulcers (IUPs) requires addressing diverse microenvironments. A pressing challenge is to effectively enhance the regenerative microenvironment at different stages of the healing process, tailoring interventions as needed. Here, a dual enzyme mimetic and bacterial responsive self-activating antimicrobial hydrogel designed to enhance IPUs healing is introduced. This hydrogel incorporates pH-responsive dual enzyme-active nanoplatforms (HNTs-Fe-Ag) encapsulated within a methacrylate-modified silk fibroin (SFMA) and dopamine methacrylamide (DMA) matrix. This composite hydrogel exhibits adaptive microenvironment regulation capabilities. Under the low pH microenvironment of bacterial infection, it has excellent antimicrobial activity by self-activating the •OH generation in conjunction with photothermal effects. Under the neutral and alkaline microenvironment of chronic inflammation, it catalyzes the decomposition of hydrogen peroxide (H 2 O 2 ) to produce oxygen (O 2 ), thereby alleviating hypoxia and scavenging reactive oxygen species (ROS), which in turn remodulates the phenotype of macrophages. The composite hydrogel demonstrates on-demand therapeutic effects in the microenvironment of infected wounds, significantly enhancing the regenerative microenvironment of IUPs by promoting wound closure, inflammation regulation, and collagen deposition through self-activated antimicrobial action during infection and adaptive hypoxia relief during recovery. This approach offers a novel strategy for developing smart wound dressings.
研究领域:
伤口愈合
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生物医学工程
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纳米技术
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材料科学
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感染控制
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再生医学
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DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2025
·
IF 5.5
Yuying Niu,Zihui Yan,Siqi Yang,Yuhui Wang,Xin Wang,Chaoqing Li,Yang Bai,Jianhao Wang,Honglei Shi,Donghui Zhao
The evolution of antibiotic resistance poses a great challenge to the bacterial infectious disease therapy. Although antimicrobial peptides and photodynamic therapy have great potential in the treatment of bacteria, their clinical application is limited due to high toxicity and low therapeutic efficiency. Herein, an innovative nano antibacterial agent was designed based on cationic antimicrobial peptides (AMPs) modified with cholesterol succinate to load the hydrophobic photosensitizer TCPP (ACT) for selective killing of S. aureus. The modification of cholesterol succinate significantly increased the positive charge of AMPs while decreasing toxicity and hemolysis. The increased positive charge could capture bacteria through electrostatic interaction, which reduced the distance between the photosensitizer and bacteria to enhance the photodynamic sterilization effect. ACT selectively killed S. aureus, not E. coli, and showed excellent destruction and inhibition ability for S. aureus-formed biofilm. ACT accelerated wound healing by promoting collagen precipitation and angiogenesis after good bacterial clearance in mice with S. aureus-infected wounds. This strategy provides a paradigm for addressing toxicity and broadening the application of antimicrobial peptides and photosensitizers.
研究领域:
微生物学
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药理学
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生物医学工程
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DOI
高影响因子
TALANTA
·
2024
·
IF 5.6
Hongmin Gao,Hehua Zhang,Xue Qi,Meng Miao,Longbin Que,Xin Gu,Dong Chang,Hongzhi Pan
Accurate and reliable detection of Staphylococcus aureus ( S. aureus ) is essential for preventing infections, particularly in healthcare and food safety contexts. This work presents a novel dual-mode biosensor that integrates the CRISPR/Cas12a system with an enzyme-free isothermal amplification method for detecting S. aureus . Hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) amplify the aptamer-triggered response, significantly enhancing sensitivity. CRISPR/Cas12a′s nuclease activity is utilized in two modes: cis cleavage generates a fluorescence signal, while trans cleavage produces an electrochemical signal, enabling dual-mode detection. The biosensor demonstrates outstanding performance, with a limit of detection (LOD) as low as 5.7 CFU mL −1 in electrochemical mode and 133.7 CFU mL −1 in fluorescence mode, showcasing excellent accuracy, stability, and sensitivity. It has been successfully applied to detecting actual samples, confirming its practical applicability. This innovative approach offers a powerful tool for the swift and precise identification of S. aureus and paves the way for developing next-generation dual-mode biosensors for various analytes. Future research will aim to simplify the detection process further, making it more accessible for use in resource-limited settings.
研究领域:
分子生物学
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病原体检测
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生物传感技术
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Qianwei Qu,Xingyu Huang,Zhenxin Zhu,Jun Wang,Mengmeng Zhao,Wenqiang Cui,Yadan Zheng,Yanyan Liu,Xueying Chen,Zhiyun Zhang,Na Dong,Chunliu Dong,Yanhua Li
Background Staphylococcus aureus is an opportunistic pathogen capable of readily forming biofilms, which can result in life-threatening infections involving different organs. Sanguinarine are benzo[c]phenanthridine alkaloids extracted from the Sanguinaria canadensis L. (Papaveraceae), which have a wide range of biological activities. Previous reports have shown that sanguinarine is able to induce an elevation of ROS to exert an anti- S. aureus effect. Nevertheless, the specific mechanism of action of sanguinarine against S. aureus biofilms remains unexplored. Purpose The objective of this study was to elucidate the target site of sanguinarine in S. aureus , as well as to investigate its mechanism of antimicrobial action and its interference with biofilm formation. Additionally, the study aimed to provide further evidence supporting the use of sanguinarine as an alternative to traditional antibiotics. Methods Initially, we assessed the in vitro anti- S. aureus properties of sanguinarine through a series of methodologies, including MIC assays, time-dependent assays, and resistance development studies. Secondly, we explored the antimicrobial mechanism of sanguinarine using TEM, membrane permeability assays, and membrane fluidity assays. Subsequently, the mechanism by which sanguinarine interferes with S. aureus biofilm formation was preliminarily analyzed in vitro . Additionally, the interaction between sanguinarine and imidazoleglycerol-phosphate dehydratase (IGPD) was investigated using bio-layer interferometry assays, circular dichroism spectroscopy, molecular docking, and site-directed mutagenesis to further elucidate the role of sanguinarine in biofilm disruption. Finally, the therapeutic efficacy of sanguinarine was evaluated in vivo using mouse models of biofilm and bacteremia. Results Herein, sanguinarine demonstrated notable antimicrobial properties and interfering effects on biofilm formation. Mechanistic investigations revealed that sanguinarine exerts its antimicrobial action by dissipating the proton motive force in bacteria and compromising the integrity and functionality of the cytoplasmic membrane. Furthermore, sanguinarine was found to regulate IGPD expression and inhibit L-histidine synthesis, thereby interfering S. aureus biofilm formation. Consequently, due to its polypharmacological effect, sanguinarine significantly reduced the S. aureus load in mouse organs and the formation of biofilm on the surface of implants in vivo without any resistance. Conclusions In this study, we demonstrated that sanguinarine can exert antibacterial and interfere with biofilm formation by disrupting the cell membrane of S. aureus and targeting IGPD. These findings suggest that sanguinarine holds potential for further development as a novel antibiotic to combat biofilm-associated infections.
研究领域:
微生物学
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药理学
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感染与免疫
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DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2025
·
IF 6.6
Yebo Zhu,Tao Jiang,Ziyan Mao,Xiaodi Wang,Junli Zhu,Haixia Lu
This study focuses on the inactivation efficiency and mechanism of curcumin-mediated Photodynamic Inactivation Technology (PDI) enhanced by citric acid against Staphylococcus aureus . The inactivation effect of PDI on Staphylococcus aureus was assessed using a colony counting method, morphological changes were observed via scanning electron microscopy (SEM), and the levels of reactive oxygen species (ROS) and the activities of catalase (CAT), superoxide dismutase (SOD), adenosine triphosphatase (ATPase), and alkaline phosphatase (AKP) were measured using a microplate reader. Additionally, the degree of DNA damage was analyzed through agarose gel electrophoresis. The results demonstrated that with increasing curcumin concentration, extended illumination time, and the addition of 0.5 mg/mL citric acid, the bactericidal effect of PDI on Staphylococcus aureus was significantly enhanced ( P < 0.05). When Staphylococcus aureus was treated with 2 μmol/L curcumin combined with 0.5 mg/mL citric acid and exposed to light for 2 minutes, the total colony count in PBS decreased to 0.01% of the initial value. The photosensitizer curcumin, activated by blue light, generated highly oxidative ROS, leading to a rapid increase in ROS levels within the bacterial cells, reduced activity of intracellular antioxidant enzymes (CAT, SOD), decreased ATPase activity, increased AKPase activity in the supernatant, severe bacterial deformation, and the fading or disappearance of DNA bands, ultimately resulting in cell death. Therefore, curcumin-mediated PDI exhibits a significant inactivation effect on Staphylococcus aureus , with the synergistic effect of citric acid being particularly prominent.
研究领域:
微生物学
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生物技术
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药理学
·
细菌学
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DOI
高影响因子
危险品化学品经营许可证（带存储）