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
Methicillin-resistant Staphylococcus aureus(MRSA)represents a significant global public health threat.Combination therapy,particularly the use of antibiotics in conjunction with non-antibiotic agents,has emerged as a ...Methicillin-resistant Staphylococcus aureus(MRSA)represents a significant global public health threat.Combination therapy,particularly the use of antibiotics in conjunction with non-antibiotic agents,has emerged as a promising strategy to address the growing crisis of antibiotic resistance.Fosfomycin(FOS),increasingly utilized in clinical practice for treating drug-resistant bacterial infections,exhibits limited efficacy as a monotherapy.Here,we find that 5-fluorouracil(5-FU),an US Food and Drug Administration(FDA)-approved anticancer drug,effectively enhances the antibacterial activity of FOS against MRSA,including biofilm-embedded MRSA cells.Mechanistically,5-FU targets cytidine triphosphate(CTP)synthase,a rate-limiting enzyme responsible for the adenosine triphosphate(ATP)-dependent conversion of uridine triphosphate(UTP)to CTP.Moreover,we demonstrate that the synergistic effect of 5-FU and FOS arises from the perturbation of pyrimidine metabolism,which induces membrane damage,dissipation of the proton motive force(PMF),enhanced ATP synthesis,and accumulation of reactive oxygen species,culminating in bacterial death.In both Galleria mellonella(G.mellonella)and murine infection models,the combination of 5-FU and FOS markedly improves survival and reduces bacterial burdens.Collectively,our work demonstrates the therapeutic potential of 5-FU combined with FOS for tackling MRSA infections and highlights the pivotal role of perturbing pyrimidine metabolism in restoring antibiotic susceptibility.展开更多
The emergence of drug-resistant bacterial infection and persistent biofilm colonization pose a rigorous challenge to effective wound healing and regeneration,necessitating the innovative therapeutic strategies to comb...The emergence of drug-resistant bacterial infection and persistent biofilm colonization pose a rigorous challenge to effective wound healing and regeneration,necessitating the innovative therapeutic strategies to combat these pressing clinical crises.Herein,nortriptyline,a novel United States Food and Drug Administration(FDA)-approved tricyclic antidepressant was uncovered to effectively potentiate bactericidal activities ofβ-lactam antibiotics against methicillin-resistant Staphylococcus aureus(MRSA).Mechanistically,nortriptyline functions by disrupting the microbial iron homeostasis and potentiation of Fenton chemistry-mediated oxidative stress,concomitant with metabolic reprogramming via tricarboxylic acid(TCA)cycle dysregulation and membrane destabilization.To enhance combination therapy-mediated therapeutic potential in wound management,the dual-loaded self-healing hydrogel OHA-PLL@AN was engineered to exhibit excellent biocompatibility and antibacterial potentials through molecular cross-linking of oxidized hyaluronic acid(OHA)andε-polylysine(PPL).The therapeutic efficacy of OHA-PLL@AN was further validated in a murine model with MRSA-infected cutaneous wounds.OHA-PLL@AN therapy significantly attenuated the inflammatory response,concurrently promoting angiogenesis and accelerating the cutaneous wounds healing.Collectively,these findings underscore the dual drug-loaded self-healing hydrogel OHA-PLL@AN with anti-infection and anti-inflammatory properties as a novel therapeutic strategy for drug-resistant bacterial infected wounds therapy.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
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
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
new sesquiterpene-lactone,designated as neopentalenolactone D1(1),was isolated from the fermentation cultures of Streptomyces aureus SP-371,which is known for producing agricultural-bactericide aureonuclemycin.The che...new sesquiterpene-lactone,designated as neopentalenolactone D1(1),was isolated from the fermentation cultures of Streptomyces aureus SP-371,which is known for producing agricultural-bactericide aureonuclemycin.The chemical structure of compound 1 was determined to be a neopentapyrrole natural product with a 5/5/6 tricyclic skeleton and one amide functional group,by using spectroscopic techniques such as nuclear magnetic resonance(1D/2D NMR)and high-resolution mass spectrometry(HR-ESI-MS).Its structural information indicates that it is probably the shunt product of neopentalenolactone biosynthetic pathway.In antibacterial activity evaluations,compound 1 demonstrated no inhibitory effects against the tested strains including Escherichia coli(DH5a),Staphylococcus aureus,and Bacillus subtilis under the experimental conditions.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
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
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
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 National Natural Science Foundation of China(32222084 and 32172907)the Key R&D Program of Jiangsu Province(Modern Agriculture)(BE2023332)+2 种基金the Jiangsu Agricultural Science and Technology Innovation Fund(CX(24)3072)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the 111 Project D18007。
摘要Methicillin-resistant Staphylococcus aureus(MRSA)represents a significant global public health threat.Combination therapy,particularly the use of antibiotics in conjunction with non-antibiotic agents,has emerged as a promising strategy to address the growing crisis of antibiotic resistance.Fosfomycin(FOS),increasingly utilized in clinical practice for treating drug-resistant bacterial infections,exhibits limited efficacy as a monotherapy.Here,we find that 5-fluorouracil(5-FU),an US Food and Drug Administration(FDA)-approved anticancer drug,effectively enhances the antibacterial activity of FOS against MRSA,including biofilm-embedded MRSA cells.Mechanistically,5-FU targets cytidine triphosphate(CTP)synthase,a rate-limiting enzyme responsible for the adenosine triphosphate(ATP)-dependent conversion of uridine triphosphate(UTP)to CTP.Moreover,we demonstrate that the synergistic effect of 5-FU and FOS arises from the perturbation of pyrimidine metabolism,which induces membrane damage,dissipation of the proton motive force(PMF),enhanced ATP synthesis,and accumulation of reactive oxygen species,culminating in bacterial death.In both Galleria mellonella(G.mellonella)and murine infection models,the combination of 5-FU and FOS markedly improves survival and reduces bacterial burdens.Collectively,our work demonstrates the therapeutic potential of 5-FU combined with FOS for tackling MRSA infections and highlights the pivotal role of perturbing pyrimidine metabolism in restoring antibiotic susceptibility.
基金supported by the National Natural Science Foundation of China(Grant Nos.:U24A20453,U23A20242 and 32503106)China Postdoctoral Science Foundation(Grant Nos.:2024T170330,2024M751096 and GZB20240268).
摘要The emergence of drug-resistant bacterial infection and persistent biofilm colonization pose a rigorous challenge to effective wound healing and regeneration,necessitating the innovative therapeutic strategies to combat these pressing clinical crises.Herein,nortriptyline,a novel United States Food and Drug Administration(FDA)-approved tricyclic antidepressant was uncovered to effectively potentiate bactericidal activities ofβ-lactam antibiotics against methicillin-resistant Staphylococcus aureus(MRSA).Mechanistically,nortriptyline functions by disrupting the microbial iron homeostasis and potentiation of Fenton chemistry-mediated oxidative stress,concomitant with metabolic reprogramming via tricarboxylic acid(TCA)cycle dysregulation and membrane destabilization.To enhance combination therapy-mediated therapeutic potential in wound management,the dual-loaded self-healing hydrogel OHA-PLL@AN was engineered to exhibit excellent biocompatibility and antibacterial potentials through molecular cross-linking of oxidized hyaluronic acid(OHA)andε-polylysine(PPL).The therapeutic efficacy of OHA-PLL@AN was further validated in a murine model with MRSA-infected cutaneous wounds.OHA-PLL@AN therapy significantly attenuated the inflammatory response,concurrently promoting angiogenesis and accelerating the cutaneous wounds healing.Collectively,these findings underscore the dual drug-loaded self-healing hydrogel OHA-PLL@AN with anti-infection and anti-inflammatory properties as a novel therapeutic strategy for drug-resistant bacterial infected wounds therapy.
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 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 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 the National Natural Science Foundation of China(No.22077134)。
摘要new sesquiterpene-lactone,designated as neopentalenolactone D1(1),was isolated from the fermentation cultures of Streptomyces aureus SP-371,which is known for producing agricultural-bactericide aureonuclemycin.The chemical structure of compound 1 was determined to be a neopentapyrrole natural product with a 5/5/6 tricyclic skeleton and one amide functional group,by using spectroscopic techniques such as nuclear magnetic resonance(1D/2D NMR)and high-resolution mass spectrometry(HR-ESI-MS).Its structural information indicates that it is probably the shunt product of neopentalenolactone biosynthetic pathway.In antibacterial activity evaluations,compound 1 demonstrated no inhibitory effects against the tested strains including Escherichia coli(DH5a),Staphylococcus aureus,and Bacillus subtilis under the experimental conditions.
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.
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.