Methicillin-resistant Staphylococcus aureus(MRSA) causes widespread infections and poses serious public health concerns. Its high level of resistance to multiple antibiotics has garnered growing interest in identifyin...Methicillin-resistant Staphylococcus aureus(MRSA) causes widespread infections and poses serious public health concerns. Its high level of resistance to multiple antibiotics has garnered growing interest in identifying and applying novel antibacterial compounds derived from natural sources. In this study, we purified a biosurfactant(BS) from Bacillus rugosus HH2 to develop a natural antibacterial agent. This agent was then reinforced with chitooligosaccharide(COS) and polyvinyl alcohol(PVA) to create a hydrogel that promoted healing in MRSA-infected wounds. The COS/PVA/BS hydrogel was readily fabricated via the freeze-thaw method and demonstrated excellent mechanical strength, biological activity,and biocompatibility. In vitro assays confirmed that the hydrogel significantly enhanced the proliferation, migration, angiogenesis, and extracellular matrix deposition of fibroblasts,keratinocytes, and endothelial cells. Moreover, it exhibited strong bacteriostatic and bactericidal activities against MRSA, along with potent antibiofilm activity and inhibition of virulence factors relevant to MRSA-induced wound infections. Its anti-virulence effects have been linked to the downregulation of quorum sensing and virulence-related genes in MRSA. In an in vivo model of MRSA-induced infection, the COS/PVA/BS hydrogel significantly accelerated wound healing and markedly reduced the MRSA burden. Immunofluorescence staining confirmed enhanced neovascularization and regulated macrophage responses,underscoring the angiogenic and immunomodulatory effects of the hydrogel. Overall,the COS/PVA/BS hydrogel represents a promising therapeutic strategy for addressing antibiotic-resistant bacterial infections and promoting wound repair, supported by the use of common raw materials, a simple fabrication process, and high-yield production of natural antibacterial agents.展开更多
Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contribu...Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contributors to staphylococcal food poisoning(SFP),causing vomiting,diarrhea,abdominal pain,headache,muscle cramps,and other acute gastroenteritis symptoms.More than 25 SEs and staphylococcal enterotoxin-like toxins(SE/s)have been described and which together comprise a superfamily of pyrogenic toxin superantigens(SAgs)[2].展开更多
The overuse of antibiotics has accelerated the emergence of resistant bacteria,posing critical threats to food safety and public health.This challenge underscores the urgent need for alternative strategies,such as ant...The overuse of antibiotics has accelerated the emergence of resistant bacteria,posing critical threats to food safety and public health.This challenge underscores the urgent need for alternative strategies,such as antivirulence therapy,which disarms pathogens by targeting virulence factors rather than inhibiting bacterial growth.In this study,we identified farrerol,a flavonoid,as a potent inhibitor of the caseinolytic peptidase P(ClpP)protease,a key virulence regulator in Staphylococcus aureus,with an IC50of 19.33μg/mL.Farrerol significantly disrupts virulence factor secretion and reduces pathogenicity,demonstrating its potential to control S.aureus-induced foodborne illnesses.Mechanistic studies using fluorescence resonance energy transfer(FRET),thermal shift assay(TSA),cellular thermal shift assay(CETSA),fluorescence quenching,and molecular docking revealed that farrerol interacts with ClpP via key residues(GLY-127,GLN-132,and ASP-170).In vivo,farrerol reduced the bacterial load and improved survival in a Galleria mellonella infection model.Our findings demonstrated that farrerol is an effective antivirulence agent,offering an innovative approach for the food industry to control S.aureus-induced foodborne infections.This approach holds great potential for enhancing food safety and mitigating antibiotic resistance.展开更多
Objective:To investigate the prevalence,antimicrobial resistance and genetic diversity of Staphylococcus(S.)aureus among healthy young adults of 18 to 25 years in Ho Chi Minh City,Vietnam.Methods:A cross-sectional,des...Objective:To investigate the prevalence,antimicrobial resistance and genetic diversity of Staphylococcus(S.)aureus among healthy young adults of 18 to 25 years in Ho Chi Minh City,Vietnam.Methods:A cross-sectional,descriptive study was conducted between December 2023 and December 2024.Nasal swabs were processed for S.aureus isolation,antibiotic susceptibility testing,and PCR-based detection of spa,pvl,and mecA genes.Genetic similarity was assessed using the unweighted pair group method with arithmetic mean cluster analysis.Statistical significance was determined by Chi-square test.Results:In this cross-sectional study of 428 students,the S.aureus carriage rate was 33.9%.Methicillin-resistant S.aureus(MRSA)prevalence was 54.5%(79/145).10%-17%of MRSA isolates exhibited resistance to three to ten antibiotics,with two strains demonstrating resistance to 11 and 12 drugs,respectively.The pvl gene was detected in 5.8%of isolates.55.17%S.aureus strains belonged to ten distinct spa types with 300-bp amplicons.Conclusions:These findings provide valuable insights into S.aureus carriage patterns among youth in Ho Chi Minh City,informing public health strategies for prevention and treatment.展开更多
E.coli O157:H7 and Staphylococcus aureus have emerged as significant foodborne pathogens,characterized by considerable incidence rates and mortality.Despite advancements,current detection methods are hindered by chall...E.coli O157:H7 and Staphylococcus aureus have emerged as significant foodborne pathogens,characterized by considerable incidence rates and mortality.Despite advancements,current detection methods are hindered by challenges in enhancing specificity and sensitivity.Herein,we introduced a cutting-edge biosensor that employs a novel CHA-coupled CRISPR multi-stage signal amplification technique for the rapid and ultra-sensitive detection of these two pathogens.This microfluidic device consisted of an upstream serpentine mixing channel and a downstream boat-shaped microcavity equipped with a microcolumn array,facilitating efficient reagent mixing,robust CHA amplification,and CRISPR reactions.Multiple signal amplification was achieved through bacterial competitive binding triggered by catalytic hairpin assembly(CHA)and cr RNA-mediated CRISPR reactions.Based on this platform,the detection of target bacteria is transformed into nucleic acid detection,with a maximum detection range of 134 CFU/mL for E.coli O157:H7 and 181 CFU/mL for Staphylococcus aureus,which were better or comparable to previously reported biosensors.The entire assay was completed within approximately 1.5 h,with a minimal sample volume requirement of just 10μL.The biosensor exhibited a high recovery rate,ranging from 95%to 115%,and demonstrated excellent specificity towards the target bacteria.In summary,this biosensor offers a rapid,accurate,and highly sensitive tool for food safety and clinical diagnostics.展开更多
BACKGROUND Staphylococcus aureus(S.aureus)is one of the six highly pathogenic nosocomial bacteria.These bacteria develop or evolve with several antibiotic resistance mechanisms and therefore known to escape antibiotic...BACKGROUND Staphylococcus aureus(S.aureus)is one of the six highly pathogenic nosocomial bacteria.These bacteria develop or evolve with several antibiotic resistance mechanisms and therefore known to escape antibiotic treatments.Several reports suggest that multidrug resistance in S.aureus is increasing worldwide over the time.Indian population is comprised of diverse ethnic group residing different geographical regions.Recent reports revealed that antibiotic resistance in S.aureus isolates vary in different regions of India.AIM To identify antibiotic resistance pattern in S.aureus in India.METHODS In the present study,we overviewed resistance in S.aureus isolates to different antibiotics.We searched for the research articles on antibiotic resistance in S.aureus from India using Scopus,Google scholar,and PubMed databases(Prospero registration No.PROSPERO 2025CRD420251153034).We identified a total of 26 articles published during 2013 to 2024 in English language.We extracted the information about the location of the study,antibiotics used and percentage of the resistant isolates.RESULTS Among 26 studies,most of the studies were reported from northern India(31%),southern India(27%)and eastern India(27%),followed by western India(11%)and Pan India(4%).The findings highlight very high resistance to beta-lactam antibiotics,particularly penicillin and methicillin,reflecting a substantial burden of methicillinresistant S.aureus.Fluoroquinolones and macrolides also showed elevated resistance levels,whereas linezolid,teicoplanin,chloramphenicol,and doxycycline retained comparatively better activity.CONCLUSION The present review,demonstrated geographical region wise trends of antibiotic resistance in S.aureus from India,which will be useful in designing the further studies investigating antibiotic resistance patterns.展开更多
Zinc oxide(ZnO)nanoparticles are widely used in topical products,including cosmetics and sunscreens,because of their ultraviolet-protective and antibacterial properties.Although ZnO nanoparticles are generally conside...Zinc oxide(ZnO)nanoparticles are widely used in topical products,including cosmetics and sunscreens,because of their ultraviolet-protective and antibacterial properties.Although ZnO nanoparticles are generally considered to have low toxicity in healthy skin,their safety profile remains uncertain because they can generate reactive oxygen species and induce oxidative stress.Staphylococcus aureus,a common skin commensal,can cause inflammation and barrier dysfunction,contributing to conditions such as atopic dermatitis.Despite the frequent use of ZnO nanoparticles and the ubiquitous presence of S.aureus on the skin,the health effects of their simultaneous exposure remain poorly understood.This study investigated the effects of ZnO nanoparticles on HaCaT keratinocytes when applied alone or in combination with S.aureus,focusing on oxidative stress,barrier integrity,inflammation,and apoptosis.ZnO nanoparticles induced oxidative stress,disrupted barrier integrity,triggered inflammatory responses,and promoted apoptosis associated with mitochondrial dysfunction.Co-exposure to ZnO nanoparticles and S.aureus further intensified these effects.Additional analyses revealed that activation of the mitogen-activated protein kinase pathway contributed to this enhanced response.These findings indicate that the biological impact of ZnO nanoparticles differs in the presence of skin microbiota compared with exposure alone.This study provides a revised perspective for evaluating the health risks of ZnO-based formulations and offers mechanistic insights useful for designing therapeutic strategies targeting S.aureus-associated skin disorders.展开更多
Objective This study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis(AD),a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction...Objective This study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis(AD),a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction.A key focus was screening traditional Chinese medicine(TCM)active components with dual antibacterial and antipruritic efficacy,followed by systematic evaluation of their in vitro antibacterial activity.Additionally,a novel drug delivery system was constructed to enable localized efficient drug delivery,inhibiting S.aureus proliferation and alleviating its induced pruritus,thereby providing new strategies for targeted AD therapy.Methods Male C57BL/6J mice aged 6-8 weeks(body weight 18-22 g)were used to establish an AD model via repeated oxazolone sensitization.On day 14,microbial samples were collected from the lesional area(1 cm²)using sterile cotton swabs,followed by vortex mixing,serial dilution,and plating on 5%sheep blood agar plates(incubated at 37℃ for 24 h).Single colonies with complete transparentβ-hemolytic zones were isolated and identified as vancomycin-intermediate S.aureus(VISA)via 16S rRNA sequencing.An S.aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension(McFarland turbidity 0.1)to the nape and back skin of mice.The pruritic phenotype and inflammatory cell infiltration induced by S.aureus were evaluated using comprehensive approaches including behavioral assays(e.g.,scratching frequency recording),hematoxylin-eosin(HE)staining,and toluidine blue staining.The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B(PAB)and double network hydrogel(DN)was separately assessed by disk diffusion assay,while the minimum inhibitory concentration(MIC)of PAB was determined via broth dilution method.Further validation of the pharmacodynamic characteristics of the composite system(PAB@DN,composed of PAB and DN)was conducted through behavioral assays,HE staining,and dermatitis scoring,with its drug release profile evaluated by mass spectrometry analysis.Based on scratching behavioral analysis and dermatitis scoring,the optimal ratio and concentration of PAB@DN were optimized.Results The S.aureus load in AD lesional tissues was significantly higher than in normal skin((5.3±0.33)×10⁶CFU vs.(3.6±0.26)×10⁷CFU,P<0.001).In the S.aureus mono-infection group,mice exhibited a 6.7-fold increase in scratching frequency compared to the control group.HE staining revealed marked epidermal thickening((10.4±2.39)μm vs.(85.6±1.95)μm,P<0.0001),and toluidine blue staining showed a 23-fold increase in mast cell degranulation.Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect on S.aureus growth,with its in vitro antibacterial effect being 57%that of the antibiotic cefepime(inhibition zone diameter:PAB(1.885±0.036)cm vs.cefepime(3.636±0.005)cm,P<0.0001)and a minimum inhibitory concentration(MIC)of 1 g/L.The carrier double network hydrogel(DN)itself lacked direct antibacterial activity(no significant difference in inhibition zone diameter compared to the control)but effectively ameliorated the dry symptoms of AD-like lesions.The PAB@DN composite system demonstrated a synergistic effect compared to individual components,resulting in a 50%reduction in scratching behavior,an 86%decrease in dermatitis score,and a 60%reduction in epidermal thickening.It also reduced the S.aureus load in mouse skin by approximately 34%,with the optimal effective formulation being PAB at 1 g/L loaded onto DN.Conclusion S.aureus colonization plays a critical driving role in the onset and progression of AD.Using an S.aureus infection model,this study confirmed that the pseudolaric acid B-hydrogel composite delivery system(PAB@DN)can effectively alleviate S.aureus-induced pruritus and skin damage,providing experimental evidence for microbiota-targeted therapy of AD.展开更多
To investigate the intervention effect of human-derived Staphylococcus epidermidis on skin inflammation,thirty-seven skin swab samples were collected from the Guangzhou,China.Strains of Staphylococcus were isolated an...To investigate the intervention effect of human-derived Staphylococcus epidermidis on skin inflammation,thirty-seven skin swab samples were collected from the Guangzhou,China.Strains of Staphylococcus were isolated and purified using selective culture media,followed by species identification through 16S rRNA sequencing and phylogenetic tree construction.The antioxidant activity of the isolated strains was assessed via antioxidant assays.Furthermore,an inflammatory model with high pyroptosis expression in BJ cells was established using lipopolysaccharide(LPS)induction to evaluate the inhibitory effect of the isolates on the pyroptosis pathway.A strain of human-derived Staphylococcus epidermidis was isolated and named M-5Y.Following fermentation,the resulting supernatant exhibited potent free radical scavenging capacity against both DPPH and ABTS,indicating substantial antioxidant activity.Furthermore,the M-5Y supernatant significantly suppressed the activation of the pyroptosis pathway in BJ cells triggered by LPS,demonstrating notable anti-inflammatory efficacy.展开更多
[Objectives]This study aimed to evaluate the detection sensitivity of Staphylococcus aureus in dairy products utilizing the chip digital PCR(cdPCR)technique.[Methods]Specific primers and probes were designed and synth...[Objectives]This study aimed to evaluate the detection sensitivity of Staphylococcus aureus in dairy products utilizing the chip digital PCR(cdPCR)technique.[Methods]Specific primers and probes were designed and synthesized based on the conserved sequence of the heat-resistant nuclease gene nuc of S.aureus.cdPCR was employed to detect S.aureus,and the sensitivity of this technique was systematically assessed in samples exhibiting low levels of contamination.[Results]cdPCR demonstrated precise quantification when the initial concentration of the sample enrichment solution was equal to or greater than 50 CFU/mL.The detection dynamic range extended across at least five orders of magnitude,with a minimum DNA detection limit of 0.2304 pg/μL.In artificially contaminated cheese samples,the method s lower limit of quantification for detecting S.aureus was 8×102 CFU/g.Regression analysis demonstrated that the gene copy number concentration measured by cdPCR exhibited a strong linear correlation with bacterial contamination concentration across a broad range.[Conclusions]The cdPCR method developed in this study demonstrates high sensitivity and robust quantitative capabilities,offering a reliable technical approach for the precise detection of low-level S.aureus contamination in dairy products.展开更多
Background:Staphylococcus aureus bacteremia is associated with high mortality.Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S.aureus bacteremia ...Background:Staphylococcus aureus bacteremia is associated with high mortality.Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S.aureus bacteremia is unclear.Methods:In an ongoing international Bayesian adaptive platform trial,we conducted an open-label,randomized comparison of cefazolin with an antistaphylococcal penicillin(flucloxacillin or cloxacillin)in adult patients with penicillin-resistant,methicillin-susceptible S.aureus bacteremia.The primary outcome,which was evaluated with a hierarchical Bayesian logistic-regression model,was death from any cause within 90 days after enrollment in the platform.We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin(with the criterion for noninferiority prespecified as an adjusted odds ratio of<1.2,which approximates an absolute difference in mortality of<2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%),as well as the posterior probability of superiority(with the criterion of an adjusted odds ratio of<1.0).Secondary safety outcomes included the development of acute kidney injury within 14 days.Results:This domain of the ongoing trial was conducted between February 17,2022,and August 7,2024,by which time the criterion for noninferiority had been met.Mortality at 90 days among adults who could be evaluated was 15.0%(97 deaths among 645 patients)in the cefazolin group and 17.0%(109 deaths among 642 patients)in the antistaphylococcal-penicillin group(adjusted odds ratio,0.81;95%credible interval,0.59 to 1.12;probability of noninferiority,99.2%;probability of superiority,89.8%).Acute kidney injury occurred in 92 of 660 patients(13.9%)in the cefazolin group,as compared with 127 of 648(19.6%)in the antistaphylococcal-penicillin group(adjusted odds ratio,0.67;95%credible interval,0.50 to 0.89;probability of superiority,99.7%).Conclusions:In patients with methicillin-susceptible S.aureus bacteremia,cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury.(Funded by the National Health and Medical Research Council and others;SNAP ClinicalTrials.gov number,NCT05137119.).展开更多
Background Mastitis caused by Staphylococcus aureus(S.aureus)is one of the most intractable problems for the dairy industry,causing significantly reduced milk yields and early slaughter of cows worldwide.MicroRNAs(miR...Background Mastitis caused by Staphylococcus aureus(S.aureus)is one of the most intractable problems for the dairy industry,causing significantly reduced milk yields and early slaughter of cows worldwide.MicroRNAs(miRNAs)can post-transcriptionally regulate gene expression and studies in recent years have shown the importance of miRNA-associated gene regulation in S.aureus-induced mastitis.Results In this study,to investigate the role of miR-223 in mastitis,we performed experiments to overexpress and suppress miR-223 in an immortalized bovine mammary epithelial cell line(MAC-T)infected with S.aureus.Overexpression of miR-223 in MAC-T cells repressed cell apoptosis and necrosis induced by S.aureus infection,whereas suppression of miR-223 had the opposite effect.Transcriptome expression profiling with weighted gene co-expression network analysis(WGCNA)and gene set variation analysis(GSVA)showed that miR-223 affects apoptosis and inflammation-related pathways.Furthermore,differentially expressed(DE)genes were evaluated,and genes exhibiting contrasting expression trends in the miR-223 overexpressed and suppressed groups were assessed as potential target genes of miR-223.Potential target genes,including CDC25B,PTPRF,DCTN1,and DPP9,were observed to be associated with apoptosis and necroptosis.Finally,through integrative analysis of genome-wide association study(GWAS)data and the animal quantitative trait loci(QTL)database,we determined that target genes of miR-223 were significantly enriched in single-nucleotide polymorphisms(SNP)and QTLs related to somatic cell count(SCC)and mastitis.Conclusion In summary,miR-223 has an inhibitory effect on S.aureus-induced cell apoptosis and necrosis by regulating PTPRF,DCTN1,and DPP9.These genes were significantly enriched in QTL regions associated with bovine mastitis resistance,underscoring their relevance in genetic regulation of disease resilience.Our findings provide critical genetic markers for enhancing mastitis resistance,particularly S.aureus-induced mastitis,through selective breeding.This work offers valuable insights for developing cattle with improved resistance to mastitis via targeted genetic selection.展开更多
Although coagulase-negative Staphylococcus(CNS),along with technological activities,plays a key role in fermented sausage flavour and nutrient production,the molecular mechanism of these activities remains elusive.In ...Although coagulase-negative Staphylococcus(CNS),along with technological activities,plays a key role in fermented sausage flavour and nutrient production,the molecular mechanism of these activities remains elusive.In this study,18 CNS strains with high proteolytic activity were isolated from Chinese Dong fermented pork(Nanx Wudl),and their technological and transcriptomic properties were investigated.After biochemical identification and genetic analysis,their technological properties,including nitrate reductase,catalase,antioxidant,and lipolytic activities and their growth under varying temperatures,salt concentrations,and p H levels were evaluated.Their aroma-producing potential was also determined in a model medium resembling fermented sausages.Transcriptomic analysis was performed using the most promising isolates.Biochemical identification and 16S rDNA sequencing revealed that the 18 Staphylococcus strains belonged to Staphylococcus xylosus,Staphylococcus saprophyticus,Staphylococcus carnosus,Staphylococcus sciuri,and Staphylococcus equorum.In terms of technological properties,16 strains showed a nitrate-reducing ability,while 11 strains had a lipolytic activity.All strains exhibited superoxide dismutase(SOD)and catalase activities;four strains displayed an SOD activity of>50%.They also tolerated 10%NaCl and 150 mg/kg of nitrite.They showed significant differences in ketone and acid production.The transcriptomic analysis of S.xylosus strains Sx3 and Sx6,which were selected because of their excellent enzymatic activities and aroma-producing ability,revealed the remarkable effect of genes related to pyruvate catabolism and amino acid metabolism on aroma generation.Therefore,this study provided valuable insights into the metabolic mechanisms underlying the technological properties of CNS and identified promising candidates as starter cultures in fermented sausage manufacturing.展开更多
Addressing the uncontrolled spread and increase in antibiotic resistance in methicillin-resistant Staphylococcus aureus(MRSA)will require new control strategies,particularly to improve the safety of food.Our results r...Addressing the uncontrolled spread and increase in antibiotic resistance in methicillin-resistant Staphylococcus aureus(MRSA)will require new control strategies,particularly to improve the safety of food.Our results revealed the efficacy of theaflavin-3,3′-digallate(TFBG),which is a novel polyphenol derived from tea,in targeting the key regulatory protein multiple gene regulator A(MgrA)in S.aureus.Through fluorescence anisotropy,we showed that the half maximal inhibitory concentration(IC50)of TFBG was 26.76μg/mL.TFBG uniquely counters S.aureus by regulating its virulence factors and adhesion processes rather than by killing the bacteria directly.This compound alters the expression of key virulence factors and modulates the transcription levels of genes related to adhesion in S.aureus,ultimately reducing the bacteria’s ability to adhere to fibrinogen and its hemolytic activity.Our assays confirmed that TFBG directly interacts with the MgrA protein in MRSA,and we identified critical binding sites.Our in vivo studies highlighted the potent efficacy of TFBG.TFBG administration is an innovative approach to improve food safety by diminishing MRSA virulence and reducing its pathogenicity.展开更多
Staphylococcus aureus infection is a global public health problem,searching and developing green alternatives for antibiotics are urgently required.In this study,the exopolysaccharides(EPS)produced by Lactobacillus he...Staphylococcus aureus infection is a global public health problem,searching and developing green alternatives for antibiotics are urgently required.In this study,the exopolysaccharides(EPS)produced by Lactobacillus helveticus WXD191 were extracted and purified.Structure analysis suggested that the EPS contained Ara,Man,Gal,GalN,Glc,GlcN,and GlcA,with a molecular of 84.2 kDa.Methylation combined with nuclear magnetic resonance(NMR)spectroscopy analysis revealed that the backbone of EPS (was→3)-β-D-Galp-(1→3)-β-D-GlcpNAc-(1→4)-β-D-GlcpA-(1→3-Man-1→2-Man-1→2,6-Man-1→2,6-Man-1→).Congo red analysis and circular dichroism(CD)spectrum indicated the existence ofα-helices.Crystalline characteristics,scanning electron microscopy,and thermogravimetric analysis revealed that EPS formed thermally stable amorphous with a small amount of microcrystalline structure and a rough and porous surface.Meanwhile,the S.aureus bloodstream infection model was used to evaluate the protection efficiency for systemic infection induced by S.aureus and found that the EPS could enhance survival as well as reduce bacterial burden and proinflammatory chemokines.Collectively,these results suggested that EPS isolated from L.helveticus was a competitive candidate for defense against S.aureus infection.展开更多
Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacill...Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.展开更多
Objective:To explore the effect of a hydrogel of Piper longum(P.longum)root against biofilm-forming multidrug-resistant(MDR)Staphylococcus aureus(S.aureus)through in vitro,in silico,and in vivo studies.Methods:We isol...Objective:To explore the effect of a hydrogel of Piper longum(P.longum)root against biofilm-forming multidrug-resistant(MDR)Staphylococcus aureus(S.aureus)through in vitro,in silico,and in vivo studies.Methods:We isolated the P.longum root ethanolic extract and the compounds using p-HPLC.In vitro antibacterial and antibiofilm activities of P.longum root extract and isolated alkamide compounds against biofilm-forming MDR S.aureus(ATCC 33591)were assessed using agar diffusion and broth microdilution methods,respectively.In silico investigations were conducted to investigate the interaction of alkamide compounds with three target proteins glycogen synthase kinase 3β(GSK3β),matrix metalloproteinases-8(MMP-8),and inducible nitric oxide synthase(iNOS).In addition,the wound healing effect of P.longum root extract 2%and 5%(w/v)-containing hydrogels was determined in mice.Results:The ethanolic root extract of P.longum and its compounds exhibited in vitro antibacterial activity with minimum inhibitory concentrations between 50µg/mL and 700µg/mL,as well as significantly reduced biofilm formation.Piperdardine isolated from P.longum root extract had the best molecular docking score(-9.7,-9.8,and-9.2 kcal/mol)with target proteins GSK3β,MMP-8,and iNOS.In vivo studies showed that P.longum hydrogels significantly lowered the number of colony-forming units(P<0.05).The P.longum 5%(w/v)hydrogel-treated group showed enhanced wound healing activity,achieving a wound contraction rate of 99.34%on day 14.Furthermore,histopathological analysis confirmed increased re-epithelialization and reduced inflammation in mice treated with P.longum 5%(w/v)hydrogel.Conclusions:P.longum root extract has pharmacological potential as an antibacterial and wound-healing agent,and further research is required to confirm its efficacy and clinical application.展开更多
Background:In view of the ever-increasing representation of Staphylococcus spp.strains resistant to various antibiotics,the development of in vivo models for evaluation of novel antimicrobials is of utmost importance....Background:In view of the ever-increasing representation of Staphylococcus spp.strains resistant to various antibiotics,the development of in vivo models for evaluation of novel antimicrobials is of utmost importance.Methods:In this article,we describe the development of a fully immunocompetent porcine model of extensive skin and soft tissue damage suitable for testing topical anti-microbial agents that matches the real clinical situation.The model was developed in three consecutive stages with protocols for each stage amended based on the results of the previous one.Results:In the final model,10 excisions of the skin and underlying soft tissue were created in each pig under general anesthesia,with additional incisions to the fascia performed at the base of the defects and immediately inoculated with Staphylococcus aureus suspension.One pig was not inoculated and used as the negative control.Subsequently,the bandages were changed on Days 4,8,11,and 15.At these time points,a filter paper imprint technique(FPIT)was made from each wound for semi-quantitative microbiological evaluation.Tissue samples from the base of the wound together with the adjacent intact tissue of three randomly selected defects of each pig were taken for microbiological,histopathological,and molecular-biological examination.The infection with the inoculated S.aureus strains was sufficient during the whole experiment as confirmed by both FPIT and from tissue samples.The dynamics of the inflammatory markers and clinical signs of infection are also described.Conclusions:A successfully developed porcine model is suitable for in vivo testing of novel short-acting topical antimicrobial agents.展开更多
The use of natural products as antibiotic adjuvants to enhance efficacy and mitigate resistance is increasingly recog-nized as a promising strategy.This study explored five novel synergistic antimicrobial combinations...The use of natural products as antibiotic adjuvants to enhance efficacy and mitigate resistance is increasingly recog-nized as a promising strategy.This study explored five novel synergistic antimicrobial combinations(SACs)of carvac-rol(CARV)and three already identified SACs of thymol(THY)with chloramphenicol,gentamicin,and streptomycin against Staphylococcus aureus and Acinetobacter baumannii,critical WHO-listed pathogens,and investigated their mechanisms of action and resistance-prevention capabilities.Despite being isomers,CARV and THY exhibited distinct synergistic effects and fractional inhibitory concentration index(FICI)values depending on the antibiotic and bac-terial species.The SACs significantly reduced the required antibiotic dose by 4-to 16-fold,with FICI values ranging from 0.25 to 0.5.Growth kinetics revealed that SACs completely inhibited planktonic bacterial growth,outperform-ing antibiotics alone.Additionally,the SACs demonstrated efficacy in both inhibiting and eradicating biofilms of S.aureus and A.baumannii.Resistance development studies highlighted that neither THY nor CARV induced resistance in these pathogens.Moreover,SACs combining aminoglycosides with THY reduced the emergence of resistance in A.baumannii by up to 32-fold.In S.aureus,THY mitigated gentamicin resistance by 16-fold.CARV exhibited similar,albeit slightly less potent,effects.Mechanistic investigations revealed that THY and CARV exert antimicrobial action by multiple mechanisms,includ-ing bacterial membrane depolarization and disruption,efflux pump inhibition,disrupting ATP metabolism and miti-gating oxidative stress induced by antibiotics.These findings highlight the potential of SACs to enhance antibiotic efficacy while preventing resistance,positioning them as strong candidates for innovative antimicrobial therapies against multidrug-resistant pathogens.展开更多
Staphylococcus aureus (S. aureus) is a bacterial pathogen for humans and animals. These bacteria can resist against many antibiotics and this resistance constitute an alarming worldwide human health threat due to the ...Staphylococcus aureus (S. aureus) is a bacterial pathogen for humans and animals. These bacteria can resist against many antibiotics and this resistance constitute an alarming worldwide human health threat due to the morbidity and mortality. Phage therapy is one of the alternative treatments. The aim of this study was to isolate and characterize lytic phages of S. aureus from different wastewater sources in Bobo-Dioulasso, Burkina Faso. Eight strains of S. aureus were isolated from different clinical samples and were used to isolate phages. The isolation and host range of phages were done by the spot test. Phages were purified by the double-layer method. Similar phages after the determination of the host range were characterized using restriction enzymes. A total of 27 phages were obtained after isolation and purification. Nine of the 27 isolates reported a broad host range (≥67%). The results of enzymatic digestion allowed to consider that all phage isolates that presented the same host range and the same genetic fingerprint are the same phage strain;whereas phages that presented the same host range and different genetic fingerprints are different phage strains. Thus, a total of 15 distinct phages isolates specific to S. aureus were characterized. This study highlighted the abundance and lytic capacity of phages isolated from wastewater from Bobo-Dioulasso’s environment against clinical strains of S. aureus. The lytic capacity of these Staphyphages could be an effective alternative tool to combat bacteria multi-resistance.展开更多
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education (RS-2021-NR060118,RS-2024-00408404, and RS-2025-00555808)supported by the Korea Institute of Marine Science&Technology Promotion (KIMST)funded by the Ministry of Oceans and Fisheries (RS-2024-00404977)。
摘要Methicillin-resistant Staphylococcus aureus(MRSA) causes widespread infections and poses serious public health concerns. Its high level of resistance to multiple antibiotics has garnered growing interest in identifying and applying novel antibacterial compounds derived from natural sources. In this study, we purified a biosurfactant(BS) from Bacillus rugosus HH2 to develop a natural antibacterial agent. This agent was then reinforced with chitooligosaccharide(COS) and polyvinyl alcohol(PVA) to create a hydrogel that promoted healing in MRSA-infected wounds. The COS/PVA/BS hydrogel was readily fabricated via the freeze-thaw method and demonstrated excellent mechanical strength, biological activity,and biocompatibility. In vitro assays confirmed that the hydrogel significantly enhanced the proliferation, migration, angiogenesis, and extracellular matrix deposition of fibroblasts,keratinocytes, and endothelial cells. Moreover, it exhibited strong bacteriostatic and bactericidal activities against MRSA, along with potent antibiofilm activity and inhibition of virulence factors relevant to MRSA-induced wound infections. Its anti-virulence effects have been linked to the downregulation of quorum sensing and virulence-related genes in MRSA. In an in vivo model of MRSA-induced infection, the COS/PVA/BS hydrogel significantly accelerated wound healing and markedly reduced the MRSA burden. Immunofluorescence staining confirmed enhanced neovascularization and regulated macrophage responses,underscoring the angiogenic and immunomodulatory effects of the hydrogel. Overall,the COS/PVA/BS hydrogel represents a promising therapeutic strategy for addressing antibiotic-resistant bacterial infections and promoting wound repair, supported by the use of common raw materials, a simple fabrication process, and high-yield production of natural antibacterial agents.
基金supported by the Ministry of Science and Technology of the People’s Republic of China(2022YFD1800400).
摘要Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contributors to staphylococcal food poisoning(SFP),causing vomiting,diarrhea,abdominal pain,headache,muscle cramps,and other acute gastroenteritis symptoms.More than 25 SEs and staphylococcal enterotoxin-like toxins(SE/s)have been described and which together comprise a superfamily of pyrogenic toxin superantigens(SAgs)[2].
基金supported by the Jilin Provincial Natural Science Foundation(20220101286JC)the National Natural Science Foundation of China,General Program(32273058).
摘要The overuse of antibiotics has accelerated the emergence of resistant bacteria,posing critical threats to food safety and public health.This challenge underscores the urgent need for alternative strategies,such as antivirulence therapy,which disarms pathogens by targeting virulence factors rather than inhibiting bacterial growth.In this study,we identified farrerol,a flavonoid,as a potent inhibitor of the caseinolytic peptidase P(ClpP)protease,a key virulence regulator in Staphylococcus aureus,with an IC50of 19.33μg/mL.Farrerol significantly disrupts virulence factor secretion and reduces pathogenicity,demonstrating its potential to control S.aureus-induced foodborne illnesses.Mechanistic studies using fluorescence resonance energy transfer(FRET),thermal shift assay(TSA),cellular thermal shift assay(CETSA),fluorescence quenching,and molecular docking revealed that farrerol interacts with ClpP via key residues(GLY-127,GLN-132,and ASP-170).In vivo,farrerol reduced the bacterial load and improved survival in a Galleria mellonella infection model.Our findings demonstrated that farrerol is an effective antivirulence agent,offering an innovative approach for the food industry to control S.aureus-induced foodborne infections.This approach holds great potential for enhancing food safety and mitigating antibiotic resistance.
基金supported by Nguyen Tat Thanh University,Ho Chi Minh city,Viet Nam,grant number 2023.01.18/KHCNUniversity of Medicine and Pharmacy at Ho Chi Minh City,Vietnam,project number 214/2023/HD-DHYD.
摘要Objective:To investigate the prevalence,antimicrobial resistance and genetic diversity of Staphylococcus(S.)aureus among healthy young adults of 18 to 25 years in Ho Chi Minh City,Vietnam.Methods:A cross-sectional,descriptive study was conducted between December 2023 and December 2024.Nasal swabs were processed for S.aureus isolation,antibiotic susceptibility testing,and PCR-based detection of spa,pvl,and mecA genes.Genetic similarity was assessed using the unweighted pair group method with arithmetic mean cluster analysis.Statistical significance was determined by Chi-square test.Results:In this cross-sectional study of 428 students,the S.aureus carriage rate was 33.9%.Methicillin-resistant S.aureus(MRSA)prevalence was 54.5%(79/145).10%-17%of MRSA isolates exhibited resistance to three to ten antibiotics,with two strains demonstrating resistance to 11 and 12 drugs,respectively.The pvl gene was detected in 5.8%of isolates.55.17%S.aureus strains belonged to ten distinct spa types with 300-bp amplicons.Conclusions:These findings provide valuable insights into S.aureus carriage patterns among youth in Ho Chi Minh City,informing public health strategies for prevention and treatment.
基金supported by Natural Science Foundation of Guangdong Province,China(No.2022A1515011437)。
摘要E.coli O157:H7 and Staphylococcus aureus have emerged as significant foodborne pathogens,characterized by considerable incidence rates and mortality.Despite advancements,current detection methods are hindered by challenges in enhancing specificity and sensitivity.Herein,we introduced a cutting-edge biosensor that employs a novel CHA-coupled CRISPR multi-stage signal amplification technique for the rapid and ultra-sensitive detection of these two pathogens.This microfluidic device consisted of an upstream serpentine mixing channel and a downstream boat-shaped microcavity equipped with a microcolumn array,facilitating efficient reagent mixing,robust CHA amplification,and CRISPR reactions.Multiple signal amplification was achieved through bacterial competitive binding triggered by catalytic hairpin assembly(CHA)and cr RNA-mediated CRISPR reactions.Based on this platform,the detection of target bacteria is transformed into nucleic acid detection,with a maximum detection range of 134 CFU/mL for E.coli O157:H7 and 181 CFU/mL for Staphylococcus aureus,which were better or comparable to previously reported biosensors.The entire assay was completed within approximately 1.5 h,with a minimal sample volume requirement of just 10μL.The biosensor exhibited a high recovery rate,ranging from 95%to 115%,and demonstrated excellent specificity towards the target bacteria.In summary,this biosensor offers a rapid,accurate,and highly sensitive tool for food safety and clinical diagnostics.
摘要BACKGROUND Staphylococcus aureus(S.aureus)is one of the six highly pathogenic nosocomial bacteria.These bacteria develop or evolve with several antibiotic resistance mechanisms and therefore known to escape antibiotic treatments.Several reports suggest that multidrug resistance in S.aureus is increasing worldwide over the time.Indian population is comprised of diverse ethnic group residing different geographical regions.Recent reports revealed that antibiotic resistance in S.aureus isolates vary in different regions of India.AIM To identify antibiotic resistance pattern in S.aureus in India.METHODS In the present study,we overviewed resistance in S.aureus isolates to different antibiotics.We searched for the research articles on antibiotic resistance in S.aureus from India using Scopus,Google scholar,and PubMed databases(Prospero registration No.PROSPERO 2025CRD420251153034).We identified a total of 26 articles published during 2013 to 2024 in English language.We extracted the information about the location of the study,antibiotics used and percentage of the resistant isolates.RESULTS Among 26 studies,most of the studies were reported from northern India(31%),southern India(27%)and eastern India(27%),followed by western India(11%)and Pan India(4%).The findings highlight very high resistance to beta-lactam antibiotics,particularly penicillin and methicillin,reflecting a substantial burden of methicillinresistant S.aureus.Fluoroquinolones and macrolides also showed elevated resistance levels,whereas linezolid,teicoplanin,chloramphenicol,and doxycycline retained comparatively better activity.CONCLUSION The present review,demonstrated geographical region wise trends of antibiotic resistance in S.aureus from India,which will be useful in designing the further studies investigating antibiotic resistance patterns.
摘要Zinc oxide(ZnO)nanoparticles are widely used in topical products,including cosmetics and sunscreens,because of their ultraviolet-protective and antibacterial properties.Although ZnO nanoparticles are generally considered to have low toxicity in healthy skin,their safety profile remains uncertain because they can generate reactive oxygen species and induce oxidative stress.Staphylococcus aureus,a common skin commensal,can cause inflammation and barrier dysfunction,contributing to conditions such as atopic dermatitis.Despite the frequent use of ZnO nanoparticles and the ubiquitous presence of S.aureus on the skin,the health effects of their simultaneous exposure remain poorly understood.This study investigated the effects of ZnO nanoparticles on HaCaT keratinocytes when applied alone or in combination with S.aureus,focusing on oxidative stress,barrier integrity,inflammation,and apoptosis.ZnO nanoparticles induced oxidative stress,disrupted barrier integrity,triggered inflammatory responses,and promoted apoptosis associated with mitochondrial dysfunction.Co-exposure to ZnO nanoparticles and S.aureus further intensified these effects.Additional analyses revealed that activation of the mitogen-activated protein kinase pathway contributed to this enhanced response.These findings indicate that the biological impact of ZnO nanoparticles differs in the presence of skin microbiota compared with exposure alone.This study provides a revised perspective for evaluating the health risks of ZnO-based formulations and offers mechanistic insights useful for designing therapeutic strategies targeting S.aureus-associated skin disorders.
摘要Objective This study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis(AD),a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction.A key focus was screening traditional Chinese medicine(TCM)active components with dual antibacterial and antipruritic efficacy,followed by systematic evaluation of their in vitro antibacterial activity.Additionally,a novel drug delivery system was constructed to enable localized efficient drug delivery,inhibiting S.aureus proliferation and alleviating its induced pruritus,thereby providing new strategies for targeted AD therapy.Methods Male C57BL/6J mice aged 6-8 weeks(body weight 18-22 g)were used to establish an AD model via repeated oxazolone sensitization.On day 14,microbial samples were collected from the lesional area(1 cm²)using sterile cotton swabs,followed by vortex mixing,serial dilution,and plating on 5%sheep blood agar plates(incubated at 37℃ for 24 h).Single colonies with complete transparentβ-hemolytic zones were isolated and identified as vancomycin-intermediate S.aureus(VISA)via 16S rRNA sequencing.An S.aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension(McFarland turbidity 0.1)to the nape and back skin of mice.The pruritic phenotype and inflammatory cell infiltration induced by S.aureus were evaluated using comprehensive approaches including behavioral assays(e.g.,scratching frequency recording),hematoxylin-eosin(HE)staining,and toluidine blue staining.The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B(PAB)and double network hydrogel(DN)was separately assessed by disk diffusion assay,while the minimum inhibitory concentration(MIC)of PAB was determined via broth dilution method.Further validation of the pharmacodynamic characteristics of the composite system(PAB@DN,composed of PAB and DN)was conducted through behavioral assays,HE staining,and dermatitis scoring,with its drug release profile evaluated by mass spectrometry analysis.Based on scratching behavioral analysis and dermatitis scoring,the optimal ratio and concentration of PAB@DN were optimized.Results The S.aureus load in AD lesional tissues was significantly higher than in normal skin((5.3±0.33)×10⁶CFU vs.(3.6±0.26)×10⁷CFU,P<0.001).In the S.aureus mono-infection group,mice exhibited a 6.7-fold increase in scratching frequency compared to the control group.HE staining revealed marked epidermal thickening((10.4±2.39)μm vs.(85.6±1.95)μm,P<0.0001),and toluidine blue staining showed a 23-fold increase in mast cell degranulation.Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect on S.aureus growth,with its in vitro antibacterial effect being 57%that of the antibiotic cefepime(inhibition zone diameter:PAB(1.885±0.036)cm vs.cefepime(3.636±0.005)cm,P<0.0001)and a minimum inhibitory concentration(MIC)of 1 g/L.The carrier double network hydrogel(DN)itself lacked direct antibacterial activity(no significant difference in inhibition zone diameter compared to the control)but effectively ameliorated the dry symptoms of AD-like lesions.The PAB@DN composite system demonstrated a synergistic effect compared to individual components,resulting in a 50%reduction in scratching behavior,an 86%decrease in dermatitis score,and a 60%reduction in epidermal thickening.It also reduced the S.aureus load in mouse skin by approximately 34%,with the optimal effective formulation being PAB at 1 g/L loaded onto DN.Conclusion S.aureus colonization plays a critical driving role in the onset and progression of AD.Using an S.aureus infection model,this study confirmed that the pseudolaric acid B-hydrogel composite delivery system(PAB@DN)can effectively alleviate S.aureus-induced pruritus and skin damage,providing experimental evidence for microbiota-targeted therapy of AD.
摘要To investigate the intervention effect of human-derived Staphylococcus epidermidis on skin inflammation,thirty-seven skin swab samples were collected from the Guangzhou,China.Strains of Staphylococcus were isolated and purified using selective culture media,followed by species identification through 16S rRNA sequencing and phylogenetic tree construction.The antioxidant activity of the isolated strains was assessed via antioxidant assays.Furthermore,an inflammatory model with high pyroptosis expression in BJ cells was established using lipopolysaccharide(LPS)induction to evaluate the inhibitory effect of the isolates on the pyroptosis pathway.A strain of human-derived Staphylococcus epidermidis was isolated and named M-5Y.Following fermentation,the resulting supernatant exhibited potent free radical scavenging capacity against both DPPH and ABTS,indicating substantial antioxidant activity.Furthermore,the M-5Y supernatant significantly suppressed the activation of the pyroptosis pathway in BJ cells triggered by LPS,demonstrating notable anti-inflammatory efficacy.
基金Supported by Science and Technology Program of Inner Mongolia Autonomous Region"Research and Demonstration of Novel Molecular Biological Identification Technology for Multiple Source Components in Milk and Dairy Products"(2025YFSH0029).
摘要[Objectives]This study aimed to evaluate the detection sensitivity of Staphylococcus aureus in dairy products utilizing the chip digital PCR(cdPCR)technique.[Methods]Specific primers and probes were designed and synthesized based on the conserved sequence of the heat-resistant nuclease gene nuc of S.aureus.cdPCR was employed to detect S.aureus,and the sensitivity of this technique was systematically assessed in samples exhibiting low levels of contamination.[Results]cdPCR demonstrated precise quantification when the initial concentration of the sample enrichment solution was equal to or greater than 50 CFU/mL.The detection dynamic range extended across at least five orders of magnitude,with a minimum DNA detection limit of 0.2304 pg/μL.In artificially contaminated cheese samples,the method s lower limit of quantification for detecting S.aureus was 8×102 CFU/g.Regression analysis demonstrated that the gene copy number concentration measured by cdPCR exhibited a strong linear correlation with bacterial contamination concentration across a broad range.[Conclusions]The cdPCR method developed in this study demonstrates high sensitivity and robust quantitative capabilities,offering a reliable technical approach for the precise detection of low-level S.aureus contamination in dairy products.
摘要Background:Staphylococcus aureus bacteremia is associated with high mortality.Whether cefazolin or an antistaphylococcal penicillin should be preferred for the treatment of methicillin-susceptible S.aureus bacteremia is unclear.Methods:In an ongoing international Bayesian adaptive platform trial,we conducted an open-label,randomized comparison of cefazolin with an antistaphylococcal penicillin(flucloxacillin or cloxacillin)in adult patients with penicillin-resistant,methicillin-susceptible S.aureus bacteremia.The primary outcome,which was evaluated with a hierarchical Bayesian logistic-regression model,was death from any cause within 90 days after enrollment in the platform.We assessed the posterior probability of the noninferiority of cefazolin to flucloxacillin or cloxacillin(with the criterion for noninferiority prespecified as an adjusted odds ratio of<1.2,which approximates an absolute difference in mortality of<2.5 percentage points if mortality in the antistaphylococcal-penicillin group is 15%),as well as the posterior probability of superiority(with the criterion of an adjusted odds ratio of<1.0).Secondary safety outcomes included the development of acute kidney injury within 14 days.Results:This domain of the ongoing trial was conducted between February 17,2022,and August 7,2024,by which time the criterion for noninferiority had been met.Mortality at 90 days among adults who could be evaluated was 15.0%(97 deaths among 645 patients)in the cefazolin group and 17.0%(109 deaths among 642 patients)in the antistaphylococcal-penicillin group(adjusted odds ratio,0.81;95%credible interval,0.59 to 1.12;probability of noninferiority,99.2%;probability of superiority,89.8%).Acute kidney injury occurred in 92 of 660 patients(13.9%)in the cefazolin group,as compared with 127 of 648(19.6%)in the antistaphylococcal-penicillin group(adjusted odds ratio,0.67;95%credible interval,0.50 to 0.89;probability of superiority,99.7%).Conclusions:In patients with methicillin-susceptible S.aureus bacteremia,cefazolin was noninferior to flucloxacillin or cloxacillin with respect to 90-day mortality and was associated with a lower incidence of acute kidney injury.(Funded by the National Health and Medical Research Council and others;SNAP ClinicalTrials.gov number,NCT05137119.).
基金supported by the National Key Research and Development Program of China(Grant No.2023YFF1000902,2021YFD1200903)the National Science Foundation for Young Scientists of China(Grant No.32302706)the Beijing Dairy Industry Innovation Team(Grant No.BAIC06).
摘要Background Mastitis caused by Staphylococcus aureus(S.aureus)is one of the most intractable problems for the dairy industry,causing significantly reduced milk yields and early slaughter of cows worldwide.MicroRNAs(miRNAs)can post-transcriptionally regulate gene expression and studies in recent years have shown the importance of miRNA-associated gene regulation in S.aureus-induced mastitis.Results In this study,to investigate the role of miR-223 in mastitis,we performed experiments to overexpress and suppress miR-223 in an immortalized bovine mammary epithelial cell line(MAC-T)infected with S.aureus.Overexpression of miR-223 in MAC-T cells repressed cell apoptosis and necrosis induced by S.aureus infection,whereas suppression of miR-223 had the opposite effect.Transcriptome expression profiling with weighted gene co-expression network analysis(WGCNA)and gene set variation analysis(GSVA)showed that miR-223 affects apoptosis and inflammation-related pathways.Furthermore,differentially expressed(DE)genes were evaluated,and genes exhibiting contrasting expression trends in the miR-223 overexpressed and suppressed groups were assessed as potential target genes of miR-223.Potential target genes,including CDC25B,PTPRF,DCTN1,and DPP9,were observed to be associated with apoptosis and necroptosis.Finally,through integrative analysis of genome-wide association study(GWAS)data and the animal quantitative trait loci(QTL)database,we determined that target genes of miR-223 were significantly enriched in single-nucleotide polymorphisms(SNP)and QTLs related to somatic cell count(SCC)and mastitis.Conclusion In summary,miR-223 has an inhibitory effect on S.aureus-induced cell apoptosis and necrosis by regulating PTPRF,DCTN1,and DPP9.These genes were significantly enriched in QTL regions associated with bovine mastitis resistance,underscoring their relevance in genetic regulation of disease resilience.Our findings provide critical genetic markers for enhancing mastitis resistance,particularly S.aureus-induced mastitis,through selective breeding.This work offers valuable insights for developing cattle with improved resistance to mastitis via targeted genetic selection.
基金the financial support of the National Natural Science Foundation of China(32102016)the Taishan Industrial Experts Program。
摘要Although coagulase-negative Staphylococcus(CNS),along with technological activities,plays a key role in fermented sausage flavour and nutrient production,the molecular mechanism of these activities remains elusive.In this study,18 CNS strains with high proteolytic activity were isolated from Chinese Dong fermented pork(Nanx Wudl),and their technological and transcriptomic properties were investigated.After biochemical identification and genetic analysis,their technological properties,including nitrate reductase,catalase,antioxidant,and lipolytic activities and their growth under varying temperatures,salt concentrations,and p H levels were evaluated.Their aroma-producing potential was also determined in a model medium resembling fermented sausages.Transcriptomic analysis was performed using the most promising isolates.Biochemical identification and 16S rDNA sequencing revealed that the 18 Staphylococcus strains belonged to Staphylococcus xylosus,Staphylococcus saprophyticus,Staphylococcus carnosus,Staphylococcus sciuri,and Staphylococcus equorum.In terms of technological properties,16 strains showed a nitrate-reducing ability,while 11 strains had a lipolytic activity.All strains exhibited superoxide dismutase(SOD)and catalase activities;four strains displayed an SOD activity of>50%.They also tolerated 10%NaCl and 150 mg/kg of nitrite.They showed significant differences in ketone and acid production.The transcriptomic analysis of S.xylosus strains Sx3 and Sx6,which were selected because of their excellent enzymatic activities and aroma-producing ability,revealed the remarkable effect of genes related to pyruvate catabolism and amino acid metabolism on aroma generation.Therefore,this study provided valuable insights into the metabolic mechanisms underlying the technological properties of CNS and identified promising candidates as starter cultures in fermented sausage manufacturing.
摘要Addressing the uncontrolled spread and increase in antibiotic resistance in methicillin-resistant Staphylococcus aureus(MRSA)will require new control strategies,particularly to improve the safety of food.Our results revealed the efficacy of theaflavin-3,3′-digallate(TFBG),which is a novel polyphenol derived from tea,in targeting the key regulatory protein multiple gene regulator A(MgrA)in S.aureus.Through fluorescence anisotropy,we showed that the half maximal inhibitory concentration(IC50)of TFBG was 26.76μg/mL.TFBG uniquely counters S.aureus by regulating its virulence factors and adhesion processes rather than by killing the bacteria directly.This compound alters the expression of key virulence factors and modulates the transcription levels of genes related to adhesion in S.aureus,ultimately reducing the bacteria’s ability to adhere to fibrinogen and its hemolytic activity.Our assays confirmed that TFBG directly interacts with the MgrA protein in MRSA,and we identified critical binding sites.Our in vivo studies highlighted the potent efficacy of TFBG.TFBG administration is an innovative approach to improve food safety by diminishing MRSA virulence and reducing its pathogenicity.
基金funding from multiple sources including the Science and Technology Major Project of the Inner Mongolia Autonomous Region of China(2021ZD0013)the Key Scientific and Technological Research Program of Inner Mongolia Autonomous Region(2021GG0156)+1 种基金Inner Mongolia Key Laboratory for Molecular Regulation of the Cell(2021PT0002)the National Natural Science Foundation of China(32060800).
摘要Staphylococcus aureus infection is a global public health problem,searching and developing green alternatives for antibiotics are urgently required.In this study,the exopolysaccharides(EPS)produced by Lactobacillus helveticus WXD191 were extracted and purified.Structure analysis suggested that the EPS contained Ara,Man,Gal,GalN,Glc,GlcN,and GlcA,with a molecular of 84.2 kDa.Methylation combined with nuclear magnetic resonance(NMR)spectroscopy analysis revealed that the backbone of EPS (was→3)-β-D-Galp-(1→3)-β-D-GlcpNAc-(1→4)-β-D-GlcpA-(1→3-Man-1→2-Man-1→2,6-Man-1→2,6-Man-1→).Congo red analysis and circular dichroism(CD)spectrum indicated the existence ofα-helices.Crystalline characteristics,scanning electron microscopy,and thermogravimetric analysis revealed that EPS formed thermally stable amorphous with a small amount of microcrystalline structure and a rough and porous surface.Meanwhile,the S.aureus bloodstream infection model was used to evaluate the protection efficiency for systemic infection induced by S.aureus and found that the EPS could enhance survival as well as reduce bacterial burden and proinflammatory chemokines.Collectively,these results suggested that EPS isolated from L.helveticus was a competitive candidate for defense against S.aureus infection.
基金supported by research grants from the Guangdong Province Basic and Applied Basic Research Fund Project(2022A1515110447)Open Fund Project of the State Key Laboratory of Applied Microbiology in South China(SKLAM006-2022)+1 种基金74th batch of general funding from the China Postdoctoral Science Foundation(2023M740774)Guangdong Provincial People’s Hospital,Postdoctoral Research Launch Fund(BY012022017)。
摘要Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.
基金supported by NPDF fellowship grants from the Central Council for Research in Ayurvedic Sciences,Ministry of AYUSH,Govt.of India(HQ-ESTT012/60/2022-ESTT/6783).
摘要Objective:To explore the effect of a hydrogel of Piper longum(P.longum)root against biofilm-forming multidrug-resistant(MDR)Staphylococcus aureus(S.aureus)through in vitro,in silico,and in vivo studies.Methods:We isolated the P.longum root ethanolic extract and the compounds using p-HPLC.In vitro antibacterial and antibiofilm activities of P.longum root extract and isolated alkamide compounds against biofilm-forming MDR S.aureus(ATCC 33591)were assessed using agar diffusion and broth microdilution methods,respectively.In silico investigations were conducted to investigate the interaction of alkamide compounds with three target proteins glycogen synthase kinase 3β(GSK3β),matrix metalloproteinases-8(MMP-8),and inducible nitric oxide synthase(iNOS).In addition,the wound healing effect of P.longum root extract 2%and 5%(w/v)-containing hydrogels was determined in mice.Results:The ethanolic root extract of P.longum and its compounds exhibited in vitro antibacterial activity with minimum inhibitory concentrations between 50µg/mL and 700µg/mL,as well as significantly reduced biofilm formation.Piperdardine isolated from P.longum root extract had the best molecular docking score(-9.7,-9.8,and-9.2 kcal/mol)with target proteins GSK3β,MMP-8,and iNOS.In vivo studies showed that P.longum hydrogels significantly lowered the number of colony-forming units(P<0.05).The P.longum 5%(w/v)hydrogel-treated group showed enhanced wound healing activity,achieving a wound contraction rate of 99.34%on day 14.Furthermore,histopathological analysis confirmed increased re-epithelialization and reduced inflammation in mice treated with P.longum 5%(w/v)hydrogel.Conclusions:P.longum root extract has pharmacological potential as an antibacterial and wound-healing agent,and further research is required to confirm its efficacy and clinical application.
基金Supported by the Ministry of Health of the Czech Republic,Grant/Award Number:NU22-05-00475 and NV19-05-00214。
摘要Background:In view of the ever-increasing representation of Staphylococcus spp.strains resistant to various antibiotics,the development of in vivo models for evaluation of novel antimicrobials is of utmost importance.Methods:In this article,we describe the development of a fully immunocompetent porcine model of extensive skin and soft tissue damage suitable for testing topical anti-microbial agents that matches the real clinical situation.The model was developed in three consecutive stages with protocols for each stage amended based on the results of the previous one.Results:In the final model,10 excisions of the skin and underlying soft tissue were created in each pig under general anesthesia,with additional incisions to the fascia performed at the base of the defects and immediately inoculated with Staphylococcus aureus suspension.One pig was not inoculated and used as the negative control.Subsequently,the bandages were changed on Days 4,8,11,and 15.At these time points,a filter paper imprint technique(FPIT)was made from each wound for semi-quantitative microbiological evaluation.Tissue samples from the base of the wound together with the adjacent intact tissue of three randomly selected defects of each pig were taken for microbiological,histopathological,and molecular-biological examination.The infection with the inoculated S.aureus strains was sufficient during the whole experiment as confirmed by both FPIT and from tissue samples.The dynamics of the inflammatory markers and clinical signs of infection are also described.Conclusions:A successfully developed porcine model is suitable for in vivo testing of novel short-acting topical antimicrobial agents.
摘要The use of natural products as antibiotic adjuvants to enhance efficacy and mitigate resistance is increasingly recog-nized as a promising strategy.This study explored five novel synergistic antimicrobial combinations(SACs)of carvac-rol(CARV)and three already identified SACs of thymol(THY)with chloramphenicol,gentamicin,and streptomycin against Staphylococcus aureus and Acinetobacter baumannii,critical WHO-listed pathogens,and investigated their mechanisms of action and resistance-prevention capabilities.Despite being isomers,CARV and THY exhibited distinct synergistic effects and fractional inhibitory concentration index(FICI)values depending on the antibiotic and bac-terial species.The SACs significantly reduced the required antibiotic dose by 4-to 16-fold,with FICI values ranging from 0.25 to 0.5.Growth kinetics revealed that SACs completely inhibited planktonic bacterial growth,outperform-ing antibiotics alone.Additionally,the SACs demonstrated efficacy in both inhibiting and eradicating biofilms of S.aureus and A.baumannii.Resistance development studies highlighted that neither THY nor CARV induced resistance in these pathogens.Moreover,SACs combining aminoglycosides with THY reduced the emergence of resistance in A.baumannii by up to 32-fold.In S.aureus,THY mitigated gentamicin resistance by 16-fold.CARV exhibited similar,albeit slightly less potent,effects.Mechanistic investigations revealed that THY and CARV exert antimicrobial action by multiple mechanisms,includ-ing bacterial membrane depolarization and disruption,efflux pump inhibition,disrupting ATP metabolism and miti-gating oxidative stress induced by antibiotics.These findings highlight the potential of SACs to enhance antibiotic efficacy while preventing resistance,positioning them as strong candidates for innovative antimicrobial therapies against multidrug-resistant pathogens.
摘要Staphylococcus aureus (S. aureus) is a bacterial pathogen for humans and animals. These bacteria can resist against many antibiotics and this resistance constitute an alarming worldwide human health threat due to the morbidity and mortality. Phage therapy is one of the alternative treatments. The aim of this study was to isolate and characterize lytic phages of S. aureus from different wastewater sources in Bobo-Dioulasso, Burkina Faso. Eight strains of S. aureus were isolated from different clinical samples and were used to isolate phages. The isolation and host range of phages were done by the spot test. Phages were purified by the double-layer method. Similar phages after the determination of the host range were characterized using restriction enzymes. A total of 27 phages were obtained after isolation and purification. Nine of the 27 isolates reported a broad host range (≥67%). The results of enzymatic digestion allowed to consider that all phage isolates that presented the same host range and the same genetic fingerprint are the same phage strain;whereas phages that presented the same host range and different genetic fingerprints are different phage strains. Thus, a total of 15 distinct phages isolates specific to S. aureus were characterized. This study highlighted the abundance and lytic capacity of phages isolated from wastewater from Bobo-Dioulasso’s environment against clinical strains of S. aureus. The lytic capacity of these Staphyphages could be an effective alternative tool to combat bacteria multi-resistance.