Scientific Reports
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2025
·Vol. 15
·期 1
·1-11
·
IF 3.9
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.
研究领域:
微生物学
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药理学
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感染病学
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产品关联
DOI
PubMed
高影响因子
BIOFOULING
·
2026
·
IF 2.5
Ming Lu,Ze Yao,Chunshuang Li,Xiang Li,Hui Shang,Songtao Bie
Berberine, a naturally occurring isoquinoline alkaloid, has demonstrated strong antibiofilm properties against Staphylococcus aureus. However, the molecular mechanisms underlying this activity remain poorly understood. Here, we report that berberine effectively inhibits S. aureus biofilm formation with a minimum biofilm inhibitory concentration (MBIC) of 32 µg ml–1. XTT assays demonstrated a marked reduction in biofilm metabolic activity, while high-content screening (HCS) combined with three-dimensional reconstruction revealed significant decreases in biofilm biomass and thickness. Mechanistically, berberine selectively suppressed the production of key extracellular polymeric substance (EPS) components, particularly polysaccharide intercellular adhesin (PIA) and proteins, without significantly affecting extracellular DNA (eDNA) levels. Transcriptomic profiling integrated with protein–protein interaction (PPI) network modeling suggested that srrA, a response regulator within the two-component system, may serve as a central hub gene downregulated by berberine. Quantitative PCR (qPCR) further corroborated the altered expression of srrA and associated genes (walR, atpB, luxS, icaR). Collectively, these findings provide mechanistic insights into berberine’s antibiofilm activity and point to srrA-mediated EPS regulation as a candidate pathway warranting further investigation.
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DOI
PubMed
高影响因子
BMC Pulmonary Medicine
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2025
·Vol. 25
·期 1
·1-11
·
IF 2.8
Luo Jun,Liu Min,Ai Wen,Zheng Xiaoling,Han Lu,Huang Kuo,Zhang Changlin,Wang Peng,Fan Jinhong,Li Qianyuan,Luo Chunhua
Background Timely detection of viable Staphylococcus aureus (MSSA)/ methicillin-resistant Staphylococcus aureus (MRSA) and antimicrobial resistance are crucial for the treatment of patients with pulmonary infection. Methods In the current study, we have developed and evaluated the potential clinical applicability of the PMA TaqMan-based real-time PCR (PMA-TaqMan qPCR) assay for detection of viable MSSA/MRSA and antimicrobial susceptibility directly from bronchoalveolar lavage fluid. Results The PMA-TaqMan qPCR assay demonstrated high sensitivity with a detection limit of 800 CFU/mL within 115 min. Furthermore, the assay required only 45 min of antibiotic exposure and completed antimicrobial susceptibility testing within 160 min. Upon detection of 10 spiked bronchoalveolar lavage fluid samples treated by clindamycin after 24 h, the PMA-TaqMan qPCR assay showed better agreement with culture-based methods in detecting viable bacteria. Subsequent antimicrobial susceptibility results of bronchoalveolar lavage fluid samples spiked by 16 MRSA isolates and 11 MSSA isolates based on the current assay, compared with the standard broth microdilution method, showed an overall agreement of 100% (95% confidence intervals [CI]: 80.64 to 100) for MRSA and 90.91% (95% CI: 62.27 to 98.38) for MSSA. Conclusions Our findings demonstrate that the PMA-TaqMan qPCR assay is a highly sensitive and specific method for the direct detection of viable MSSA/MRSA and antimicrobial susceptibility testing from bronchoalveolar lavage fluid.
研究领域:
微生物学
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分子诊断
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感染性疾病
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抗菌耐药
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DOI
PubMed
高影响因子
TALANTA
·
2018
·
IF 4.244
Yaqi Shan,Chunxiang Xu,Mingliang Wang,Zhu Zhu,Fu-Gen Wu,Zengliang Shi,Qiannan Cui,Gowri Manohari Arumugam
A novelty bilinear suspension immunoassay biosensor is developed for Staphylococcus aureus specific detection. In the present study, a dual-color-based sandwich immunosensor was constructed for sensitive and selective detection of this bacterium. In this bioassay system, the monoclonal antibodies of Staphylococcus aureus were immobilized on carboxyl-modified fluorescent microspheres (PSA-R6G) which acted as a capture probe. A secondary fluorescein isothiocyanate (FITC)-labelled antibody of Staphylococcus aureus acted as a sensitive reporter antibody. After dual-labelling with R6G and FITC, the enriched Staphylococcus aureus bacteria were observed by using the multiparameter flow cytometry analysis. In this method, two regression equations were obtained with I FITC = 1.56lgC + 4.50 and I R6G = 1.54lgC + 2.78, respectively. It can be noted that the two slopes were very similar, which indicated the false positives decrease significantly. For general applications, the quantificational measurements of Staphylococcus aureus in milk and water samples were also carried out. The suspension immunoassay exhibited an excellent specificity to Staphylococcus aureus in contrast to conventional culture-based method.
研究领域:
微生物学
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免疫学
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医学检测
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DOI
PubMed
高影响因子
BIOFOULING
·
2025
·
IF 2
Hui Yuan,Ming Lu,Chen Shi,Chunshuang Li,Ze Yao,Hui Shang,Xiang Li,Heshui Yu,Songtao Bie
Plumbagin, also known as 5-hydroxy-2-methyl-1,4-naphthoquinone (PLB), is a naturally occurring naphthoquinone molecule that has demonstrated strong antibacterial and antibiofilm properties against Staphylococcus aureus (S. aureus). However, the potential of PLB to eradicate mature biofilms and the underlying mechanisms involved remain unclear. In this study explored the effects of PLB on disrupting mature S. aureus biofilms, focusing on its impact on the extracellular polymeric substances (EPS) and potential mechanisms of action. Crystal violet (CV) and XTT assays demonstrated that PLB significantly reduced both the biomass and metabolic activity of mature S. aureus biofilms in a concentration-dependent manner. High-content screening (HCS) imaging demonstrated that PLB treatment induced significant alterations in the biofilm EPS architecture, leading to a substantial reduction in overall biomass and average thickness, with disruption severity correlating positively with PLB concentration. Using molecular fluorescence probing techniques, this study found that treatment with PLB resulted in a marked reduction in EPS components, including extracellular polysaccharides (PIA), proteins, and extracellular DNA (eDNA), compared to untreated controls. Molecular docking analysis revealed that PLB strongly interacts with several key S. aureus proteins involved in EPS production, such as IcaA, IcaD, IcaB, IcaC, Bap, ClfB, and CidA, particularly binding strongly to the active sites of IcaA and Bap. Furthermore, gene expression analysis indicated that PLB downregulated genes associated with biofilm EPS production. Overall, these findings suggest that PLB effectively disrupts S. aureus biofilms by targeting the EPS. These results highlight PLB as a promising candidate for targeting mature S. aureus biofilms in chronic infections.
研究领域:
微生物学
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抗菌研究
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生物膜生物学
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药学
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分子对接
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传染病学
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产品关联
DOI
PubMed
高影响因子
Life-Basel
·
2026
·Vol. 16
·期 7
·1070
·
IF 3.9
Bo-Hao Li,Rui-Hua Xu,Zulifukeer Maituersong,Chao-Feng Lai,Ting Wang,Yu-Bin Su
Staphylococcus aureusis an important zoonotic pathogen. In recent years, it has been isolated from diseased aquatic animals, causing skin ulcers and septicemia, establishing itself as an emerging pathogen in aquaculture. Rampant antibiotic use has accelerated antimicrobial resistance, a trend that has gradually curtailed the potency of conventional antibiotic therapies, underscoring the urgent need for novel therapies. Here, we screened 20 amino acids and found that exogenous proline significantly enhances the bactericidal activity of amikacin againstS. aureus. This synergistic effect extends to other aminoglycoside antibiotics, including neomycin sulfate and gentamicin, and is also effective against drug-resistant strains such as MRSA USA300. Furthermore, we evaluated the efficacy of this combination in eradicating persisters and biofilms. Mechanistically, exogenous proline potentiates amikacin-mediated killing by modulating two key bactericidal pathways. On one hand, it enhances antibiotic uptake by augmenting the proton motive force via the electron transport chain. On the other hand, it amplifies oxidative stress through a multi-pronged mechanism involving the suppression of ROS-scavenging enzymes, activation of the Fenton reaction, and reduction in intracellular nitric oxide (NO) levels, ultimately culminating in bacterial cell death. This study proposes a promising strategy for combatingS. aureusin aquaculture and healthcare-associated infections.
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DOI
高影响因子
FOOD CONTROL
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2018
·
IF 3.667
Jin-Rong Bai,Kai Zhong,Yan-Ping Wu,Grosu Elena,Hong Gao
The aim of this study was to evaluate the inhibitory activity of shikimic acid (SA) against biofilm formation of Staphylococcus aureus and to explore its potential molecular mechanism. Crystal violet staining assay showed that SA clearly reduced the biomass of the biofilm at its sub-MICs. Light microscopic images and scanning electron microscope (SEM) observations suggested that SA inhibited the biofilm adhesion on glass slides and induced apparent collapse of biofilm architecture. In addition, XTT reduction assay and confocal laser scanning microscopic images illustrated that the metabolic activity and the viability of the SA-treated biofilm cells significantly decreased. Cell mobility of the SA-treated S. aureus was also inhibited. These observations suggested that SA inhibited the initial biofilm formation by interfering the metabolic activity, the cell viability, and the cell mobility of S. aureus . However, SA failed to disrupt the one-day-old mature biofilm of S. aureus even at the concentrations higher than MIC, suggesting that SA disturbed the early steps in the biofilm formation of S. aureus . qRT-PCR analyses showed that SA down-regulated the transcription of sarA , while up-regulated the transcription of agrA , which resulted in the prevention of biofilm formation. So, SA could be a potential antibiofilm agent to inhibit biofilm formation of S. aureus .
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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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Zhibo Hu,Yujiao Zhu,Junjie Chen,Jun Chen,Chunyuan Li,Zhizeng Gao,Jing Li,Lan Liu
The emerging outbreak of bacterial diseases is a major challenge for the aquaculture industry. The development of new antibacterial agents from natural resources to curb fish bacterial diseases in aquaculture is becoming increasingly popular. In this study, eight new benzoic acid-containing alkaloids, asperalin A–F (1–6), asperalumazine A (7), and N-(3-acetamidopropyl)-3,4-dihydroxybenzamide (8), along with four known compounds (9–12) were isolated and identified from a seagrass-derived Aspergillus alabamensis. Their chemical structures were established on the basis of extensive spectroscopic analyses (including HRESIMS, 1D and 2D NMR spectroscopy), NMR computational methods, and electronic circular dichroism (ECD) calculations. Compounds 1–6 exhibited moderate or potent inhibitory activities against at least one fish pathogenic bacterium, among Edwardsiella ictalurid, Streptococcus iniae, and Streptococcus parauberis, and these compounds represent the first report of the coupling of dihydroquinolone alkaloids with benzoic acid derivatives. Compounds 3 and 4 showed strong activities against Staphylococcus aureus, S. iniae, and S. parauberis, with an MIC value of 10.1, 5.0, and 10.1 μM, respectively. Compound 5, an N-alkylated product of 4, exhibited the strongest inhibitory effects against S. iniae, with an MIC value of 2.2 μM. Notably, compound 6, as a new natural bactericide, showed moderate to potent inhibitory activity toward all strains tested, including one Gram-negative bacterium E. ictalurid (10.9 μM, MIC) and four Gram-positive bacteria S. iniae (43.6 μM, MIC), S. aureus (21.8 μM, MIC), S. parauberis (87.3 μM, MIC), and Bacillus subtilis (21.8 μM, MIC). Compound 7 represents the first example of a lumazine derivative directly coupled to a benzoic acid moiety by a hydroxymethyl group.
研究领域:
水产养殖
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微生物学
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药物化学
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天然产物
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产品关联
DOI
PubMed
高影响因子
BMC MICROBIOLOGY
·
2025
·Vol. 25
·期 1
·1-12
·
IF 4.2
Lin Fei,Jin Weiwei,Yang Longbing,Tian Chunren,Zhang Jin,Jiao Zhenglong,Peng Jian,Guo Guo
Objectives The urgent development of novel antibacterial agents to combat antibiotic-resistant Staphylococcus aureus is imperative. Antimicrobial peptides are considered promising alternatives to traditional antibiotics for addressing this pressing issue. This study investigates the antibacterial activities and potential mechanisms of the peptide HfAMP against methicillin-resistant S. aureus (MRSA). Methods The antibacterial activity of HfAMP against MRSA was evaluated using the broth microdilution method, growth curve, and time-kill assay. Its potential mechanism of action was investigated through propidium iodide, laurdan, DiSC 3 (5), 2’,7’-dichlorodihydrofluorescein diacetate, and ATP quantification assays. To assess the safety and stability of HfAMP, cytotoxicity, hemolysis, and antibacterial activity were examined under different conditions (i.e., temperatures, ions, serum, pH, and enzymes). Furthermore, a mouse skin infection model was employed to evaluate the in vivo efficacy of HfAMP. Results The results demonstrate that HfAMP exhibits bacteriostatic and bactericidal activity against MRSA, with a minimum inhibitory concentration of 4 µg/mL. It remains stable under a range of pH, temperatures, and serum, although it is susceptible to degradation by pepsin. Mechanistic investigations show that HfAMP compromises bacterial membranes by interacting with membrane components and disrupting the proton motive force, leading to metabolic disturbances. In a mouse model of MRSA-induced skin infection, HfAMP significantly reduced bacterial burden and inflammation in the affected skin tissues. Conclusion Collectively, these findings indicate that HfAMP possesses potent antibacterial activity against MRSA by compromising bacterial viability and inhibiting virulence, highlighting its potential as a promising candidate for the treatment of MRSA skin-infection.
研究领域:
微生物学
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抗生素耐药性
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肽类治疗
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传染病
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SAFETY
·
2021
·Vol. 41
·期 5
·e12918
·
IF 1.953
Yingjie Han,Wenxue Chen,Zhichang Sun
In this study, inhibitory effect of limonene on Staphylococcus aureus ( S. aureus ) and its antibacterial mechanism was explored, respectively. The results showed that limonene effectively inhibited bacterial growth at a minimum inhibitory concentration (MIC) of 20 ml/L. Scanning electron microscopy (SEM), the reduction of AKP activity and fluorescence microscope observation confirmed that limonene caused the destruction of the cell morphology and cell wall integrity of S. aureus . The reduction of MFI in fluorescein diacetate staining experiment and leakage of biological macromolecules (nucleic acids and proteins) indicated that limonene damaged the cell membrane and increased membrane permeability. Besides, the reduction of membrane potential (MP) further confirmed that the damage to membrane and the reduction of respiratory metabolic activity. Furthermore, the respiratory depression test confirmed that the pathway of limonene affecting the respiratory metabolism of S. aureus is TCA pathway, followed by EMP. In addition, the disorder of succinate dehydrogenase (SDH), malate dehydrogenase (MDH), pyruvate kinase (PK), ATPase (T-ATPase, Na + -K + -ATPase, Ca 2+ -Mg 2+ -ATPase), and ATP concentration demonstrated that limonene could result in a slowdown of metabolism and metabolic dysfunction, thus inhibiting ATP synthesis.
研究领域:
微生物学
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药理学
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细胞生物学
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生物化学
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产品关联
DOI
高影响因子
Frontiers in Microbiology
·
2021
·
IF 5.64
Zhang Xiufeng,Xiong Wenguang,Peng Xianfeng,Lu Yixing,Hao Jie,Qin Zonghua,Zeng Zhenling
Serious infections caused by multidrug-resistant Staphylococcus aureus clearly urge the development of new antimicrobial agents. Drug repositioning has emerged as an alternative approach that enables us to rapidly identify effective drugs. We first reported a guanidine compound, isopropoxy benzene guanidine, had potent antibacterial activity against S. aureus. Unlike conventional antibiotics, repeated use of isopropoxy benzene guanidine had a lower probability of resistance section. We found that isopropoxy benzene guanidine triggered membrane damage by disrupting the cell membrane potential and cytoplasmic membrane integrity. Furthermore, we demonstrated that isopropoxy benzene guanidine is capable of treating invasive MRSA infections in vivo studies. These findings provided strong evidence that isopropoxy benzene guanidine represents a new chemical lead for novel antibacterial agent against multidrug-resistant S. aureus infections.
研究领域:
微生物学
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药理学
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传染病学
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产品关联
DOI
PubMed
高影响因子
Polymers
·
2023
·Vol. 15
·期 17
·3614
·
IF 5
Siyu Lu,Fan Li,Bo Liu,Kun Yang,Feng Tian,Zhi Cheng,Sheng Ding,Kexin Hou
Staphylococcus aureus(SA) is one of the most common causes of hospital-acquired infections and foodborne illnesses and is commonly found in nature in air, dust, and water. The spread and transmission of SA aerosols in the air has the potential to cause epidemic transmission among humans and between humans and animals. To effectively provide the timely warning of SA aerosols in the atmosphere, the identification and detection of SA aerosol concentrations are required. Due to their homogeneous physicochemical properties, highly monodisperse submicron polystyrene (PS) microspheres can be used as one of the simulants of SA aerosols. In this study, 800 nm monodisperse fluorescent PS (f-PS) microspheres with fluorescence spectra and particle size distribution similar to those of SA were prepared. The 800 nm monodisperse f-PS microspheres had a fluorescence characteristic peak at 465 nm; in aerosols, 800 nm monodisperse f-PS microspheres with a similar particle size distribution to that of SA were further verified, mainly in the range of 500 nm–1000 nm; finally, it was found that the f-PS microspheres still possessed similar fluorescence characteristics after 180 days. The f-PS microspheres prepared in this study are very close to SA in terms of particle size and fluorescence properties, providing a new idea for aerosol analogs of SA.Keywords:Staphylococcus aureus;polystyrene;microsphere;monodisperse;aerosols;simulation
研究领域:
微生物学
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材料科学
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环境科学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）