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Staphylococcus aureus
FOOD CONTROL · 2024 · IF 5.6

Recovery mechanisms of ohmic heating-induced sublethally injured Staphylococcus aureus: Changes in cellular structure and applications in pasteurized milk

Han Wang,Lele Shao,Yingying Sun,Yana Liu,Bo Zou,Yijie Zhao,Yuhan Wang,Xingmin Li,Ruitong Dai

This study investigated the alterations in cellular structure of ohmic heating (OH)-induced injured Staphylococcus aureus ( S. aureus ) during repair in nutrient broth, and the potential antibacterial approach of combining OH with food bacteriostatic agents and their application in milk. Specifically, the biological properties (surface hydrophobicity, zeta potential, particle size) and indicators related to cell membrane and cell wall integrity (peptidoglycan content, activities of β-galactosidase, alkaline phosphatase, and lactate dehydrogenase) of injured S. aureus during repair were measured. Additionally, scanning electron microscope and transmission electron microscope analyses were used to observe morphological changes, and protein changes were analyzed using fourier transform infrared spectroscopy and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The results suggested that OH destroyed the biological properties and membrane structure (membrane integrity and permeability increased, cell wall integrity increased, protein and functional group of membrane were damaged) of S. aureus , which could be partially restored after repair. However, the restoration process between cell membrane and cell wall were inconsistent, and morphological changes reinforce these findings. Notably, membrane proteins and functional groups on the bacterial cell surface were difficult to repair. Also, OH combined with low doses of bacteriostatic agents is a potential method to ensure food safety. Carvacrol and low temperatures could inhibit the repair of injured bacteria in pasteurized milk; and reduce precipitate formation and putrid gas production.

CAS / MDL: 327-97-9
研究领域: 食品科学 · 微生物学 · 生物技术 · 食品安全
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MICROBIOLOGICAL RESEARCH · 2025 · IF 6.9

Pathogen-derived peptidoglycan skeleton enhances innate immune defense against Staphylococcus aureus via mTOR-HIF-1α-HK2-mediated trained immunity

Zheng Jia,Lingdi Niu,Junjie Guo,Jiaqing Wang,Hai Li,Runhang Liu,Ning Liu,Shuhe Zhang,Fang Wang,Junwei Ge

Regulation of the innate immune response may be an effective strategy to enhance Staphylococcus aureus vaccines. Based on our previous findings that the Listeria peptidoglycan skeleton (pBLP) enhances the immune response through an unknown mechanism, we hypothesized that pBLP provides protection by modulating the innate immune response via trained immunity. In vitro, pBLP increased phagocytosis and inflammatory cytokine levels and elevated the anti-inflammatory cytokine TGF-β following secondary stimulation. In an in vivo model, our findings indicate that pBLP, when administered with a vaccine, protects mice from methicillin-resistant S. aureus challenge and also provides protection against S. aureus CMCC26003 in the absence of antigens. Using an ex vivo model, we demonstrated that pBLP increases markers of trained immunity in peritoneal macrophages. Transcriptome analysis of differentially expressed genes and inhibitor experiments revealed that the trained immunity process induced by pBLP depends on mTOR-HIF-1α and hexokinase 2. This study is the first to demonstrate that pBLP can induce trained immunity. Furthermore, we show that the peptidoglycan skeleton induces a distinct trained immunity phenotype compared to β-glucan, enhancing vaccine protection. Our study provides valuable insights for the design of novel vaccines that integrate both specific and innate immune responses.

CAS / MDL: 53123-88-9
研究领域: 免疫学 · 微生物学 · 疫苗研发
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MICROCHIMICA ACTA · 2024 ·Vol. 191 ·期 7 ·1-10 · IF 5.3

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus

Gao Bao,Ding Yu,Cai Zhihe,Wu Shi,Wang Juan,Ling Na,Ye Qinghua,Chen Moutong,Zhang Youxiong,Wei Xianhu,Ye Yingwang,Wu Qingping

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus ( S. aureus ). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3′,5,5′-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 10 1 –5 × 10 5 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus -fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72–9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria. Graphical abstract

研究领域: 生物化学 · 纳米医学 · 微生物学
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JOURNAL OF MEDICINAL CHEMISTRY · 2025 · IF 6.8

Development of Membrane-Targeting Osthole Derivatives Containing Pyridinium Quaternary Ammonium Moieties with Potent Anti-Methicillin-Resistant Staphylococcus aureus Properties

Ting Xu,Zihan Xue,Xinhui Li,Miaomiao Zhang,Ruige Yang,Shangshang Qin,Yong Guo

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital- and community-acquired infections, necessitating the development of novel antibacterials. Here, we designed and synthesized 30 osthole derivatives with pyridinium quaternary ammonium moieties. In vitro bioassay showed that compounds 8u and 8ac exhibited potent antibacterial activity against S. aureus ATCC 29213 and ten clinical MRSA isolates (MIC = 0.5–1 μg/mL), with low hemolytic activity, rapid bactericidal effects, and minimal resistance induction. In MRSA-infected mouse models of skin abscesses and sepsis, 8u and 8ac also displayed excellent antibacterial effects and safety, which were comparable to vancomycin. Mechanistic studies revealed that 8u and 8ac selectively target bacterial membranes via binding to phosphatidylglycerol (PG), increasing intracellular reactive oxygen species (ROS), inducing content leakage, and ultimately causing bacterial death. These findings suggest 8u and 8ac as promising novel lead candidates for anti-MRSA drug development.

研究领域: 药理学 · 微生物学
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MICROBIAL PATHOGENESIS · 2019 · IF 2.581

Characterization of serine acetyltransferase (CysE) from methicillin-resistant Staphylococcus aureus and inhibitory effect of two natural products on CysE

Changming Chen,Qiulong Yan,Mengxing Tao,Huaying Shi,Xiuyan Han,Liqiu Jia,Yukun Huang,Lizhe Zhao,Chao Wang,Xiaochi Ma,Yufang Ma

Methicillin-resistant Staphylococcus aureus (MRSA) is a major hospital-acquired infective pathogen that has developed resistance to many antibiotics. It is imperious to develop novel anti-MRSA drugs to control the emergence of drug resistance. The biosynthesis of cysteine in bacteria is catalyzed by CysE and CysK. CysE was predicted to be important for bacterial viability , it could be a potential drug target. The serine acetyltransferase activity of CysE was detected and its catalytic properties were also determined. CysE homology model was built to investigate interaction sites between CysE and substrate L-Ser or inhibitors by molecular docking . Docking data showed that residues Asp94 and His95 were essential for serine acetyltransferase activity of CysE, which were confirmed by site-directed mutagenesis. Colorimetric assay was used to screen natural products and six compounds which inhibited CysE activity (IC 50 ranging from 29.83 μM to 203.13 μM) were found. Inhibition types of two compounds 4 (11-oxo-ebracteolatanolide B) and 30 ((4 R ,4a R )-dihydroxy-3-hydroxymethyl-7,7,10a-trimethyl-2,4,4a,5,6,6a,7,8,9,10,10a,l0b-dodecahydrophenanthro[3,2- b ]furan-2-one) on CysE were determined. Compounds 4 and 30 showed inhibitory effect on MRSA growth (MIC at 12.5 μg/ml and 25 μg/ml) and mature biofilm. The established colorimetric assay will facilitate further high-throughput screening of CysE inhibitors from different compound libraries. The compounds 4 and 30 may offer structural basis for developing new anti-MRSA drugs.

研究领域: 微生物学 · 药理学 · 分子生物学
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MOLECULES · 2022 ·Vol. 27 ·期 18 ·6009 · IF 4.927

Synthesis of a Rare Water-Soluble Silver(II)/Porphyrin and Its Multifunctional Therapeutic Effect on Methicillin-Resistant Staphylococcus aureus

Jiaqi He,Yu Yin,Yingjie Shao,Wenkai Zhang,Yanling Lin,Xiuping Qian,Qizhi Ren

Porphyrin derivatives are popular photodynamic therapy (PDT) agents; however, their typical insolubility in water has made it challenging to separate cells of organisms in a liquid water environment. Herein, a novel water-soluble 5,10,15,20-tetrakis(4-methoxyphenyl-3-sulfonatophenyl) porphyrin (TMPPS) was synthesized with 95% yield by modifying the traditional sulfonation route. The reaction of TMPPS with AgNO3afforded AgTMPPS an unusual Ag(II) oxidation state (97% yield). The free base and Ag(II) complex were characterized by matrix-assisted laser desorption ionization-mass spectroscopy, and1H nuclear magnetic resonance, Fourier-transform infrared, UV-vis, fluorescence, and X-ray photolectron spectroscopies. Upon 460 nm laser irradiation, AgTMPPS generated a large amount of1O2, whereas no ⦁OH was detected. Antibacterial experiments on methicillin-resistantStaphylococcus aureus(MRSA) revealed that the combined action of AgⅡions and PDT could endow AgTMPPS with a 100% bactericidal ratio for highly concentrated MRSA (108CFU/mL) at a very low dosage (4 μM) under laser irradiation at 360 J/cm2. Another PDT response was demonstrated by photocatalytically oxidizing 1,4-dihydronicotinamide adenine dinucleotide to NAD+with AgTMPPS. The structural features of the TMPPS and AgTMPPS molecules were investigated by density functional theory quantum chemical calculations to demonstrate the efficient chemical and photodynamical effects of AgTMPPS for non-invasive antibacterial therapy.Keywords:bivalent silver complex;sulfonated porphyrin;photodynamic therapy;photocatalytic NADH oxidation;multifunctional effect;methicillin-resistantStaphylococcus aureus

研究领域: 生物化学 · 微生物学 · 药物化学
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AMB Express · 2022 ·Vol. 12 ·期 1 ·1-15 · IF 4.126

Insights into the antimicrobial effects of ceritinib against Staphylococcus aureus in vitro and in vivo by cell membrane disruption

Liu Shasha,She Pengfei,Li Zehao,Li Yimin,Yang Yifan,Li Linhui,Zhou Linying,Wu Yong

According to a 2019 report from the Centers of Disease Control and Prevention (CDC), methicillin-resistant Staphylococcus aureus (MRSA) was listed as one of the “serious threats” that had become a global public challenge in hospitals and community. Biofilm-associated infections and refractory persisters of S. aureus also impede the effectiveness of conventional antibiotics that have greatly increased difficulty in clinical therapy. There is an urgent need to develop new antimicrobials with antibiofilm and anti-persister capacities, and drug repurposing is the most effective and most economical solution to the problem. The present study profiles the antimicrobial activity of ceritinib, a tyrosine kinase inhibitor, against S. aureus in vitro and in vivo. We investigated the antimicrobial efficacy of ceritinib against planktonic and persistent S. aureus by a time-killing kinetics assay. Then, antibiofilm effect of ceritinib was assessed by crystal violet staining and laser confocal microscope observation. Ceritinib showed biofilm inhibition and mature biofilm eradication, and possesses robust bactericidal activity against S. aureus persisters. We also evaluated antimicrobial efficacy in vivo using a subcutaneous abscess infection model. Ceritinib ameliorated infection in a subcutaneous abscess mouse model and only showed negligible systemic toxicity in vivo. Mechanism exploration was conducted by transmission electron microscopy, fluorescently labeled giant unilamellar vesicle assays, and a series of fluorescent dyes. In conclusion, we find ceritinib represents potential bactericidal activity against MRSA by disrupting cell membrane integrity and inducing reactive oxygen species production, suggesting ceritinib has the potential to treat MRSA-related infections.

研究领域: 微生物学 · 药理学 · 传染病 · 药物再利用
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BIOSENSORS & BIOELECTRONICS · 2024 · IF 10.7

MoO3/MIL-125-NH2 with boosted peroxidase-like activity for electrochemical staphylococcus aureus sensing via specific recognition of bacteriophages

Yajun Gao,Suhui Xu,Ge Guo,Yajie Li,Wenyuan Zhou,Huaxiang Li,Zhenquan Yang

Herein, novel nanozyme mimics MoO 3 /MIL-125-NH 2 were reported and conjugated with bacteriophages as a new electrochemical probe for high sensitivity and specific electrochemical detection of staphylococcus aureus . The excellent peroxidase-like activity of MoO 3 /MIL-125-NH 2 composites was attributed to the integration of MIL-125-NH 2 with MoO 3 , which can boost the generation of superoxide radicals (O• 2 – ) and thus promote the oxidation of TMB in the presence of H 2 O 2 . In this work, two bacteriophages named SapYZU04 and SapYZU10 were isolated from sewage samples by using staphylococcus aureus YZUsa12 as the host. In comparison, MoO 3 /MIL-125-NH 2 @SapYZU04 was selected as a recognition agent. The DPV current declined linearly with staphylococcus aureus YZUsa12 concentration in the range of 10 1 −10 8  CFU mL −1 , with a low detection limit of 16 CFU mL −1 (S/N = 3). 20 strains including 13 host strains and 7 non-host strains were used to evaluate the selectivity of the proposed sensor. Regardless of the differences in the degrees of lytic performance for phage SapYZU04, all selected host strains can be screened with merely the same DPV current. Host spectrum-oriented bacteriophage sensing is of great importance for the practical application of bacteriophage-based biosensors in the future.

研究领域: 生物传感 · 电化学检测 · 微生物学
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MATERIALS & DESIGN · 2024 · IF 7.6

NIR-II-amplify high-entropy MXene-based sonosensitizer as sonodynamic therapy promotes methicillin-resistant Staphylococcus aureus–Infected wound healing

Wei Song,Danyan Wang,Shuai Xiao,Xiaojun He,Wei Xiong,Jianliang Shen

The growing pace of two-dimensional (2D) transitional metal carbides and nitrides (MXenes) has become a spotlight for recent research. Similarly, the need to close the gap left by conventional antibiotics, fighting off bacterial infections, and drug resistance has become eminent. Especially, MXenes are widely used as excellent photothermal agents. However, there are limited reports on MXenes as sonosensitizer. Herein, a high-entropy MXene (HEM), TVNMC was fabricated for the generation of reactive oxide species (ROS) against Methicillin-resistance Staphylococcus aureus (MRSA). Interestingly the energy storage and conversion from the diverse composition of the TVNMC MXenes allowed the generation of ROS under US irradiation and even enhanced under Photothermal therapy. This combinatorial therapy undertook a near-total kill and eradication of MRSA with its biofilm. Moreover, TVNMC MXene simultaneously eliminated MRSA abscesses while promoting wound healing with negligible anomaly to murine tissues under sonodynamic and photothermal therapy, making the TVNMC MXene a promising sonosensitizer for possible biomedical usage. Overall, this system provides great potential for the use of high-entropy MXenes as a new type of sonosensitizer in anti-infection therapy.

研究领域: 材料科学 · 纳米技术 · 生物医学工程 · 微生物学 · 治疗学
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TALANTA · 2024 · IF 5.6

Rapid and sensitive detection of Staphylococcus aureus using a THz metamaterial biosensor based on aptamer-functionalized Fe3O4@Au nanocomposites

Wenjing Yu,Jining Li,Guorong Huang,Zhe He,Huiyan Tian,Fengxin Xie,Weidong Jin,Qing Huang,Weiling Fu,Xiang Yang

Staphylococcus aureus ( S. aureus ) poses a serious threat to global public health, necessitating the establishment of rapid and simple tools for its accurate identification. Herein, we developed a terahertz (THz) metamaterial biosensor based on aptamer-functionalized Fe 3 O 4 @Au nanocomposites for quantitative S. aureus assays in different clinical samples. Fe 3 O 4 @Au@Cys@Apt has the dual advantages of magnetism and a high refractive index in the THz range and was used to rapidly separate and enrich target bacteria in a complex environmental solution. Furthermore, conjugation to the nanocomposites significantly increased the resonance frequency shift of the THz metamaterial after target loading. Our results showed that the shifts in the metamaterial resonance frequency were linearly related to S. aureus concentrations ranging from 1.0 × 10 3 to 1.0 × 10 7  CFU/mL, with a detection limit of 4.78 × 10 2  CFU/mL. The biosensor was further applied to S. aureus detection in spiked human urine and blood with satisfactory recoveries (82.4–109.6%). Our approach also demonstrated strong concordance with traditional plate counting (R 2  = 0.99306) while significantly lowering the analysis time from 24 h to <1 h. In conclusion, the proposed biosensor can not only perform culture-free and extraction-free detection of target bacteria but can also be easily extended to the determination of other pathogenic bacteria, rendering it suitable for various bacteria-related disease diagnoses.

研究领域: 医学诊断 · 纳米技术 · 微生物学
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Antibiotics-Basel · 2026 ·Vol. 15 ·期 7 ·666 · IF 5.5

A Decision-Oriented Calibrated Screening Workflow for Tylosin Derivatives: Closed-Loop MIC Validation Against Staphylococcus aureus and Streptococcus agalactiae

Huan Liu,Yiming Liu,Na Yu,Miao An,Yaoxin Tang,Jing Qu,Xiubo Li

Background:Antimicrobial resistance among Gram-positive veterinary pathogens has increased the need for more rational and experimentally grounded strategies to prioritize tylosin derivatives for antibacterial development. This study aimed to develop and externally a calibrated, decision-oriented screening workflow for tylosin-derived antibacterial analog prioritization againstStaphylococcus aureusandStreptococcus agalactiae.Methods:Publicly available minimum inhibitory concentration (MIC) data were used to construct organism-specific multilayer perceptron models. Model performance was evaluated using a five-fold out-of-fold framework. Calibrated activity probabilities were then combined with precision-oriented thresholds and similarity-based applicability-domain constraints to define prospective Go/No-Go decisions. To examine external transferability, six synthesized tylosin derivatives (A1–A6) were prospectively predicted and subsequently tested using in vitro MIC assays.Results:Internal validation showed stronger and more stable performance forS. aureusthan forS. agalactiae. However, closed-loop external validation revealed distinct organism-specific decision behaviors. ForS. aureus, the workflow assigned Go decisions to five compounds and included the only experimentally active analog, A6, but also generated several false Go decisions for inactive analogs. ForS. agalactiae, all six compounds were classified as No-Go under the primary decision rule, whereas MIC testing showed that four analogs were experimentally active, indicating conservative under-selection in a low-data extrapolation setting.Conclusions:Calibrated probabilities and applicability-domain analysis can improve the transparency and diagnostic value of antibacterial prioritization, but they do not guarantee robust external activity prediction when training-set coverage, threshold transferability, or chemical-space representation is limited. Overall, this study provides an early-stage, risk-aware closed-loop decision-support framework for tylosin-derived analog prioritization and highlights the need for iterative model updating, probability recalibration, and larger external validation before such workflows are used as high-confidence prospective screening tools in veterinary antibacterial discovery.

CAS / MDL: 67-68-5
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ANALYTICAL CHEMISTRY · 2026 · IF 7.3

Development of a Novel Probe-Based Dual-Detection platform System for Flexible Detection of Staphylococcus aureus across Transmission Pathways

Shengyang Wang,Wenjin Hu,Yuanrong Li,Jin Qi,Yi Luo,Yaling Liu

Immunodetection plays a crucial role in the prevention and treatment of Staphylococcus aureus infections. However, existing methods often suffer from limited performance, poor quantification, and applicability due to the use of low-sensitivity, nonspecific, and nontargeted probes. To address these challenges, we identified high-affinity, specific phage-displayed nanobody probes and established a dual-detection platform that enabled accurate and flexible screening of S. aureus across diverse settings. High-affinity phage-displayed nanobodies targeting S. aureus were selected to replace the conventional probes and were randomly paired with five monoclonal antibodies to demonstrate their universality. To further enhance detection sensitivity, we synthesized and optimized a core–shell magnetic–fluorescent nanolabel (Fe3O4@PS@TQD), which outperformed traditional colorimetric and fluorescent tags. By integrating these advanced components, we established a dual-detection platform capable of qualitative detection within 10 min and quantitative analysis within 30 min, achieving superior sensitivity and applicability compared with recently reported methods and commercial kits. The system exhibited excellent specificity, reproducibility, accuracy, and stability, with a detection limit as low as 5 CFU/mL after 4 h of pre-enrichment. In summary, this study presents a novel probe-driven dual-detection platform that meets the urgent need for rapid S. aureus on-site detection in complex environments.

CAS / MDL: 25952-53-8 6066-82-6
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