Quorum sensing inhibition

  • 文章类型: Journal Article
    现代作物生产依赖于化学农药和化肥的应用,从而带来环境和经济挑战。作为回应,已经出现了对环境影响较小的替代品,例如使用有益的微生物。这些微生物,特别是植物生长促进细菌(PGPB),证明了它们增强植物生长的能力,保护免受各种压力,并减少对化学投入的需求。在PGPB中,芽孢杆菌属物种由于其适应性和商业潜力而受到关注。最近的报道强调了芽孢杆菌菌株作为抗植物病原细菌的生物防治剂,同时促进植物生长。我们还研究了拟南芥幼苗中芽孢杆菌的植物生长促进能力。在这项研究中,我们使用紫罗兰色杆菌作为模型系统,评估了各种芽孢杆菌菌株控制多种植物病原细菌和抑制群体感应的潜力。总之,我们的结果表明,芽孢杆菌属细菌具有生物技术应用的巨大潜力。这包括旨在减少农用化学品使用的发展,促进可持续农业,提高作物产量和保护。
    Modern crop production relies on the application of chemical pesticides and fertilizers causing environmental and economic challenges. In response, less environmentally impactful alternatives have emerged such as the use of beneficial microorganisms. These microorganisms, particularly plant growth-promoting bacteria (PGPB), have demonstrated their ability to enhance plant growth, protect against various stresses, and reduce the need for chemical inputs. Among the PGPB, Bacillus species have garnered attention due to their adaptability and commercial potential. Recent reports have highlighted Bacillus strains as biocontrol agents against phytopathogenic bacteria while concurrently promoting plant growth. We also examined Bacillus plant growth-promoting abilities in Arabidopsis thaliana seedlings. In this study, we assessed the potential of various Bacillus strains to control diverse phytopathogenic bacteria and inhibit quorum sensing using Chromobacterium violaceum as a model system. In conclusion, our results suggest that bacteria of the genus Bacillus hold significant potential for biotechnological applications. This includes developments aimed at reducing agrochemical use, promoting sustainable agriculture, and enhancing crop yield and protection.
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  • 文章类型: Journal Article
    金黄色葡萄球菌是引起多种感染的重要细菌,并且是医院环境中患者死亡的主要原因。诸如耐甲氧西林金黄色葡萄球菌的致病细菌的出现揭示了使用抗生素治疗细菌感染性疾病的缺点。群体感应通过信号传导过程增强金黄色葡萄球菌的生存能力。如今,针对群体感应的关键组成部分作为对抗细菌引起的感染的有希望的策略引起了人们的极大兴趣。专注于辅助基因调节因子群体感应机制是金黄色葡萄球菌最常用的抗毒力方法。群体淬灭是控制由微生物引发的疾病的常见策略,因为它降低了细菌的致病性并提高了细菌生物膜对抗生素的敏感性。从而为药物发现提供了一个有趣的前景。群体感应抑制减少选择性应激并限制抗生素抗性的出现,同时限制细菌致病性。这篇综述探讨了金黄色葡萄球菌的群体感应机制,群体感应靶标和基因调控,影响群体感应的环境因素,群体感应抑制,天然产物作为群体感应抑制剂,以及靶向金黄色葡萄球菌群体感应的新型治疗策略,作为药物开发技术来增强常规抗生素方法。
    Staphylococcus aureus is a significant bacterium responsible for multiple infections and is a primary cause of fatalities among patients in hospital environments. The advent of pathogenic bacteria such as methicillin-resistant S. aureus revealed the shortcomings of employing antibiotics to treat bacterial infectious diseases. Quorum sensing enhances S. aureus\'s survivability through signaling processes. Targeting the key components of quorum sensing has drawn much interest nowadays as a promising strategy for combating infections caused by bacteria. Concentrating on the accessory gene regulator quorum-sensing mechanism is the most commonly suggested anti-virulence approach for S.aureus. Quorum quenching is a common strategy for controlling illnesses triggered by microorganisms since it reduces the pathogenicity of bacteria and improves bacterial biofilm susceptibility to antibiotics, thus providing an intriguing prospect for drug discovery. Quorum sensing inhibition reduces selective stresses and constrains the emergence of antibiotic resistance while limiting bacterial pathogenicity. This review examines the quorum sensing mechanisms involved in S. aureus, quorum sensing targets and gene regulation, environmental factors affecting quorum sensing, quorum sensing inhibition, natural products as quorum sensing inhibitory agents and novel therapeutical strategies to target quorum sensing in S. aureus as drug developing technique to augment conventional antibiotic approaches.
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  • 文章类型: Journal Article
    大量的微生物物种倾向于交流和产生生物膜,导致许多微生物感染,抗生素耐药性,以及不同行业的经济问题。因此,先进的抗生物膜需要新的属性和目标,如法定感应通信系统。同时,群体感应抑制剂作为有前途的抗生物膜分子导致抑制特定表型表达阻断细胞间通讯,这将比传统策略更容易接受。许多天然产物被鉴定为来自不同植物的抗生物膜剂,微生物,和海洋提取物。海洋藻类是具有抗生物膜活性的广泛新型化合物的有希望的来源。藻类提取物及其代谢物,如硫酸多糖(岩藻依聚糖),类胡萝卜素(玉米黄质和叶黄素),脂质和脂肪酸(γ-亚麻酸和亚油酸),间氯单宁可以抑制细胞的附着,减少细胞生长,通过阻断相关酶干扰群体感应途径,破坏细胞外聚合物.在这次审查中,生物膜形成的机制,群体感应通路,并将讨论最近确定的海藻天然产物作为抗生物膜剂。
    A large number of microbial species tend to communicate and produce biofilm which causes numerous microbial infections, antibiotic resistance, and economic problems across different industries. Therefore, advanced anti-biofilms are required with novel attributes and targets, such as quorum sensing communication system. Meanwhile, quorum sensing inhibitors as promising anti-biofilm molecules result in the inhibition of particular phenotype expression blocking of cell-to-cell communication, which would be more acceptable than conventional strategies. Many natural products are identified as anti-biofilm agents from different plants, microorganisms, and marine extracts. Marine algae are promising sources of broadly novel compounds with anti-biofilm activity. Algae extracts and their metabolites such as sulfated polysaccharides (fucoidan), carotenoids (zeaxanthin and lutein), lipid and fatty acids (γ-linolenic acid and linoleic acid), and phlorotannins can inhibit the cell attachment, reduce the cell growth, interfere in quorum sensing pathway by blocking related enzymes, and disrupt extracellular polymeric substances. In this review, the mechanisms of biofilm formation, quorum sensing pathway, and recently identified marine algae natural products as anti-biofilm agents will be discussed.
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  • 文章类型: Journal Article
    群体感应(QS)在生物膜生活方式和抗菌素耐药性中起着核心作用,破坏这些信号通路是控制细菌致病性和毒力的有前途的策略。在这项研究中,三种结构相关的苯甲醛(4-羟基苯甲醛,使用生物报告菌株和计算模拟研究了4-羟基-3-甲氧基苯甲醛(香草醛)和4-羟基-3,5-二甲氧基苯甲醛(丁香醛))在破坏铜绿假单胞菌的las和pqs系统中的作用。此外,将这些苯甲醛与妥布霉素和环丙沙星抗生素联合使用,以评估它们在预防和根除铜绿假单胞菌生物膜中提高抗生素疗效的能力.为此,总生物量,确定了生物膜细胞的代谢活性和可培养性。体外测定结果表明芳族醛具有>80%的抑制las和pqs系统的潜力。分子对接研究支持了这些发现,揭示醛与天然配体或受体蛋白(LasR,PQSA,PQSE,PQSR)。苯甲醛被证明是毒力因子衰减剂,香草醛实现了48%的减少,在生产的绿脓苷。苯甲醛-妥布霉素组合不仅导致生物质产量减少60%,而且导致已建立的生物膜的代谢活性减少90%。当苯甲醛与环丙沙星组合时,观察到类似的结果。4-羟基苯甲醛在增加生物膜对环丙沙星的敏感性方面表现出相关作用,导致生物量减少65%。这项研究揭示了,第一次,研究的苯甲醛是有效的QS抑制剂,也是抗生素抗铜绿假单胞菌活性的增强剂。
    Quorum sensing (QS) has a central role in biofilm lifestyle and antimicrobial resistance, and disrupting these signaling pathways is a promising strategy to control bacterial pathogenicity and virulence. In this study, the efficacy of three structurally related benzaldehydes (4-hydroxybenzaldehyde, 4-hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxy-3,5-dimethoxybenzaldehyde (syringaldehyde)) in disrupting the las and pqs systems of Pseudomonas aeruginosa was investigated using bioreporter strains and computational simulations. Additionally, these benzaldehydes were combined with tobramycin and ciprofloxacin antibiotics to evaluate their ability to increase antibiotic efficacy in preventing and eradicating P. aeruginosa biofilms. To this end, the total biomass, metabolic activity and culturability of the biofilm cells were determined. In vitro assays results indicated that the aromatic aldehydes have potential to inhibit the las and pqs systems by > 80 %. Molecular docking studies supported these findings, revealing the aldehydes binding in the same pocket as the natural ligands or receptor proteins (LasR, PQSA, PQSE, PQSR). Benzaldehydes were shown to act as virulence factor attenuators, with vanillin achieving a 48 % reduction in pyocyanin production. The benzaldehyde-tobramycin combination led not only to a 60 % reduction in biomass production but also to a 90 % reduction in the metabolic activity of established biofilms. A similar result was observed when benzaldehydes were combined with ciprofloxacin. 4-Hydroxybenzaldehyde demonstrated relevant action in increasing biofilm susceptibility to ciprofloxacin, resulting in a 65 % reduction in biomass. This study discloses, for the first time, that the benzaldehydes studied are potent QS inhibitors and also enhancers of antibiotics antibiofilm activity against P. aeruginosa.
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  • 文章类型: Journal Article
    嗜水气单胞菌,革兰氏阴性人畜共患病细菌,导致鱼类养殖和免疫功能低下患者的高死亡率。本研究旨在从山茶花中提取没食子酸甲酯(MG),并评估其作为针对嗜水气单胞菌SHAe115的群体感应抑制剂(QSI)的潜力。MG减少QS相关毒力因子,包括溶血,蛋白酶,还有脂肪酶,同时损害游泳运动和生物膜形成。此外,MG下调正调节基因(ahyR,fleQ)和上调的负调节剂(litR,fleN).这凸显了MG作为A.hydrophilaSHAe115的有效QSI的承诺,推进了水产养殖和人类健康中针对感染的策略。
    Aeromonas hydrophila, a Gram-negative zoonotic bacterium, causes high mortality in fish farming and immunocompromised patients. This study aimed to extract methyl gallate (MG) from the flowers of Camellia nitidissima Chi and evaluate its potential as a quorum sensing inhibitor (QSI) against Aeromonas hydrophila SHAe 115. MG reduced QS-associated virulence factors, including hemolysis, protease, and lipase, while impairing swimming motility and biofilm formation. Additionally, MG down-regulated positive regulatory genes (ahyR, fleQ) and up-regulated negative regulators (litR, fleN). This highlights MG\'s promise as a potent QSI for A. hydrophila SHAe 115, advancing strategies against infections in aquaculture and human health.
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  • 文章类型: Journal Article
    气单胞菌物种(spp。)是众所周知的鱼类病原体,其中一些已被认为是新兴的人类病原体。这种生物能够在人类中引起广泛的疾病,从肠胃炎,伤口感染,败血症和破坏性坏死性筋膜炎。全身形式的感染通常是致命的,特别是患有潜在慢性病的患者。的确,最近的趋势表明,医院获得性气单胞菌感染的数量不断增加,尤其是在免疫受损的个体中。此外,与气单胞菌相关的抗生素耐药性在对抗鱼类和人类感染方面是一个日益严峻的挑战。抗生素耐药性的获得与气单胞菌的先天转化特性有关,包括其在物种之间以及与环境共享质粒和整合子相关基因盒的能力。因此,迫切需要替代抗生素治疗。在这种情况下,在养鱼业中已经提出了许多治疗方法并进行了广泛的研究,包括针对气单胞菌群体感应的治疗。在这次审查中,我们讨论了针对群体感应抑制的当前策略,并建议此类研究能够开发新的化疗方法来对抗耐药的气单胞菌。人类感染。关键点:•众所周知,气单胞菌获得并保持耐药性,使治疗选择有限。•群体感应是气单胞菌感染中必不可少的毒力机制。•抑制群体感应可以是对抗动物和人类中的气单胞菌感染的有效策略。
    Aeromonas species (spp.) are well-known fish pathogens, several of which have been recognized as emerging human pathogens. The organism is capable of causing a wide spectrum of diseases in humans, ranging from gastroenteritis, wound infections, and septicemia to devastating necrotizing fasciitis. The systemic form of infection is often fatal, particularly in patients with underlying chronic diseases. Indeed, recent trends demonstrate rising numbers of hospital-acquired Aeromonas infections, especially in immuno-compromised individuals. Additionally, Aeromonas-associated antibiotic resistance is an increasing challenge in combating both fish and human infections. The acquisition of antibiotic resistance is related to Aeromonas\' innate transformative properties including its ability to share plasmids and integron-related gene cassettes between species and with the environment. As a result, alternatives to antibiotic treatments are desperately needed. In that vein, many treatments have been proposed and studied extensively in the fish-farming industry, including treatments that target Aeromonas quorum sensing. In this review, we discuss current strategies targeting quorum sensing inhibition and propose that such studies empower the development of novel chemotherapeutic approaches to combat drug-resistant Aeromonas spp. infections in humans. KEY POINTS: • Aeromonas notoriously acquires and maintains antimicrobial resistance, making treatment options limited. • Quorum sensing is an essential virulence mechanism in Aeromonas infections. • Inhibiting quorum sensing can be an effective strategy in combating Aeromonas infections in animals and humans.
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  • 文章类型: Journal Article
    耐甲氧西林金黄色葡萄球菌等超级细菌的出现暴露了使用抗生素治疗微生物感染的局限性。目前,新的和令人信服的治疗方法的发现越来越多地作为传统抗生素疗法的替代品。群体感应有助于金黄色葡萄球菌通过其信号传导机制变得更加可行。近年来,作为处理细菌致病性的未来方法,针对群体感应的主要因素已经获得了广泛的关注。标准抗生素疗法旨在通过靶向特定分子来抑制生物体,并为抗生素抗性的进化提供机会。这促进了新的治疗策略的发展,如抑制群体感应,可以通过降低选择压力来限制细菌毒力,从而限制了抗生素抗性的进化。这篇综述为金黄色葡萄球菌的辅助基因调节群体感应及其通过靶向调节操纵子的基因的抑制作用提供了新的见解。Further,这篇综述全面探讨了最新报道的抑制剂及其特定靶点,并讨论了其对耐甲氧西林金黄色葡萄球菌的潜在无效替代疗法.
    The emergence of superbugs like methicillin-resistant Staphylococcus aureus exposed the limitations of treating microbial infections using antibiotics. At present, the discovery of novel and convincing therapeutic methods are being executed increasingly as possible substitutes to conventional antibiotic therapies. The quorum sensing helps Staphylococcus aureus become more viable through their signaling mechanisms. In recent years, targeting the prominent factors of quorum sensing has obtained remarkable attention as a futuristic approach to dealing with bacterial pathogenicity. The standard antibiotic therapy intends to inhibit the organism by targeting specific molecules and afford a chance for the evolution of antibiotic resistance. This prompts the development of novel therapeutic strategies like inhibiting quorum sensing that can limit bacterial virulence by decreasing the selective pressure, thereby restricting antibiotic resistance evolution. This review furnishes new insights into the accessory gene regulator quorum sensing in Staphylococcus aureus and its inhibition by targeting the genes that regulate the operon. Further, this review comprehensively explores the inhibitors reported up to date and their specific targets and discusses their potentially ineffective alternative therapy against methicillin-resistant Staphylococcus aureus.
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  • 文章类型: Journal Article
    目的:本研究调查了1,2,6-三-O-没食子酰-β-葡萄糖(TGG)的抗毒性和抗生物膜作用,从山茶花中分离出来,在ProteuspenneriALK1200上。
    结果:使用各种色谱技术从夜蛾花中分离出TGG。牛奶板测定,偶氮酪蛋白测定,胞外多糖(EPS)抑制实验表明,TGG能有效抑制关键毒力因子的产生,包括蛋白酶和EPS,在P.PenneriALK1200。此外,傅里叶变换红外光谱(FT-IR)分析表明,TGG干扰了P.penneriALK1200的细胞成分组成,可能降低细菌的致病性。此外,结晶紫测定,扫描电子显微镜(SEM),和共聚焦激光扫描显微镜(CLSM)分析表明TGG处理后生物膜形成显着减少。游泳和成群试验还表明,TGG降低了P.penneriALK1200的运动性。此外,qRT-PCR分析显示TGG下调了负责运动性和生物膜形成的阳性调节基因(hfq和flhD)的表达,在上调群体感应系统负调节因子表达的同时,bssS,在P.PenneriALK1200。
    结论:TGG表现出对P.penneriALK1200的有效抗QS和抗生物膜活性。
    OBJECTIVE: The present study investigated the anti-virulence and anti-biofilm effects of 1,2,6-tri-O-galloyl-β-ᴅ-glucose (TGG), isolated from Camellia nitidissima Chi flowers, on Proteus penneri ALK 1200.
    RESULTS: TGG was isolated from C. nitidissima Chi flowers using various chromatographic techniques. The milk plate assay, azocasein assay, and exopolysaccharides (EPS) inhibition assay revealed that TGG effectively inhibited the production of crucial virulence factors, including protease and EPS, in P. penneri ALK 1200. Furthermore, fourier transform infrared spectroscopic (FT-IR) analysis indicated that TGG interfered with the composition of P. penneri ALK 1200\'s cellular component, potentially reducing the bacteria\'s pathogenicity. In addition, crystal violet assay, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM) analysis indicated a significant reduction in biofilm formation following TGG treatment. The swimming and swarming assays also showed that TGG reduced the motility of P. penneri ALK 1200. Furthermore, the qRT-PCR assay demonstrated that TGG down-regulated the expression of positive regulatory genes (hfq and flhD) responsible for motility and biofilm formation, while up-regulating the expression of the negative regulator of the quorum sensing system, bssS, in P. penneri ALK 1200.
    CONCLUSIONS: TGG displayed potent anti-QS and anti-biofilm activity towards P. penneri ALK 1200.
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  • 文章类型: Systematic Review
    群体感应是细菌根据人口密度进行交流和调节其行为的能力。抗群体感应剂(抗QSA)是治疗耐药感染的有希望的策略,以及降低导致临床相关病原体的抗生素耐药性的选择压力。这项研究分析了产出,热点,以及针对临床相关病原体的抗QSA领域的研究趋势。
    检索并分析了来自WebofScienceCoreCollection数据库的有关抗QSA的文献。使用CiteSpace和冲积生成器等工具来可视化和解释数据。
    从1998年到2023年,与反QAS研究有关的出版物数量迅速增加,在558种期刊上发表了1,743篇文章和评论。美国是最大的捐助国和最具影响力的国家,H指数为88,高于其他国家。威廉姆斯是最有成效的作家,霍比·N是被引用次数最多的作者。微生物学前沿是最多产和被引用最多的期刊。突发检测表明,主要的前沿学科从微生物学转向,临床,分子生物学,以及其他与食品相关的生物医学领域,材料,天然产品,和多学科。在整个研究历史中,最强的爆发关键词是囊性纤维化患者,最强的爆发参考是Lee和Zhang(2015)。在最近一段时间(爆发到2023年),最强爆发关键词是银纳米粒子,最强的爆发参考是Whiteley等人。(2017)。共引网络显示,最重要的兴趣和研究方向是抗生物膜/抗毒力药物的开发,和时间线分析表明,这个方向也是最活跃的。冲积流可视化的关键概念揭示了七个时间跨度最长、持续时间至今的术语,即大肠杆菌,毒力,铜绿假单胞菌,毒力因子,细菌生物膜,基因表达,仲裁感应。综合分析表明,纳米材料,海洋天然产物,人工智能(AI)可能成为未来的热点。
    这项文献计量学研究揭示了反QSA研究的现状和趋势,可能有助于研究人员确定热门话题并探索新的研究方向。
    UNASSIGNED: Quorum sensing is bacteria\'s ability to communicate and regulate their behavior based on population density. Anti-quorum sensing agents (anti-QSA) is promising strategy to treat resistant infections, as well as reduce selective pressure that leads to antibiotic resistance of clinically relevant pathogens. This study analyzes the output, hotspots, and trends of research in the field of anti-QSA against clinically relevant pathogens.
    UNASSIGNED: The literature on anti-QSA from the Web of Science Core Collection database was retrieved and analyzed. Tools such as CiteSpace and Alluvial Generator were used to visualize and interpret the data.
    UNASSIGNED: From 1998 to 2023, the number of publications related to anti-QAS research increased rapidly, with a total of 1,743 articles and reviews published in 558 journals. The United States was the largest contributor and the most influential country, with an H-index of 88, higher than other countries. Williams was the most productive author, and Hoiby N was the most cited author. Frontiers in Microbiology was the most prolific and the most cited journal. Burst detection indicated that the main frontier disciplines shifted from MICROBIOLOGY, CLINICAL, MOLECULAR BIOLOGY, and other biomedicine-related fields to FOOD, MATERIALS, NATURAL PRODUCTS, and MULTIDISCIPLINARY. In the whole research history, the strongest burst keyword was cystic-fibrosis patients, and the strongest burst reference was Lee and Zhang (2015). In the latest period (burst until 2023), the strongest burst keyword was silver nanoparticle, and the strongest burst reference was Whiteley et al. (2017). The co-citation network revealed that the most important interest and research direction was anti-biofilm/anti-virulence drug development, and timeline analysis suggested that this direction is also the most active. The key concepts alluvial flow visualization revealed seven terms with the longest time span and lasting until now, namely Escherichia coli, virulence, Pseudomonas aeruginosa, virulence factor, bacterial biofilm, gene expression, quorum sensing. Comprehensive analysis shows that nanomaterials, marine natural products, and artificial intelligence (AI) may become hotspots in the future.
    UNASSIGNED: This bibliometric study reveals the current status and trends of anti-QSA research and may assist researchers in identifying hot topics and exploring new research directions.
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  • 文章类型: Journal Article
    背景:泡桐.(P.tomentosa)是一种中等大小的树,传统上用于中国民间医学,用于治疗传染病。它是异戊二烯化酚类化合物的丰富来源,因其有前途的生物活性而被广泛研究。
    目的:由于抗生素耐药性的增加,我们的研究调查了植物来源的天然产物,这些产物可以用新的靶标/作用模式控制金黄色葡萄球菌感染,并降低抗菌素耐药性。
    方法:将乙醇提取物分级分离并通过液相色谱法检测。通过各种生物学方法在体外详细研究了植物制剂的抗葡萄球菌作用,包括最小抑制浓度(MIC)的微量稀释方法,用于协同分析的棋盘滴定技术,膜破裂实验的荧光测量,用于群体感应抑制的自诱导物-2-介导的生物测定,并计算相对粘附的菌落形成单位。通过透射电子显微镜检查形态学。
    结果:总乙醇提取物和氯仿部分显示出128和32μg/ml的MIC,分别。Diplacol,Diplacone,和3'-O-甲基-5'-羟基双取代酮在8-16μg/ml的范围内抑制金黄色葡萄球菌的生长。与莫匹罗星和夫西地酸组合显示出协同潜力。乙醇提取物和氯仿部分破坏细胞膜91.61%和79.46%,分别,而纯化合物的活性较低。与未处理的对照相比,乙醇提取物和纯化合物将粘附细胞的数量减少至47.33-10.26%。五种经过测试的植物配方,除了Diplacone,抑制金黄色葡萄球菌的群体感应。透射电镜显示金黄色葡萄球菌细胞变形。
    结论:来自番茄果实的产品显示出单独抗金黄色葡萄球菌以及与抗生素组合的抗微生物特性。通过影响细胞内靶标,香叶黄酮提出了控制葡萄球菌感染的新方法。
    BACKGROUND: Paulownia tomentosa Steud. (P. tomentosa) is a medium-sized tree traditionally used in Chinese folk medicine for the treatment of infectious diseases. It is a rich source of prenylated phenolic compounds that have been extensively studied for their promising biological activities.
    OBJECTIVE: Due to the increasing development of antibiotic resistance, our study investigated plant-derived natural products from the fruits of P. tomentosa that could control Staphylococcus aureus infections with novel targets/modes of action and reduce antimicrobial resistance.
    METHODS: The ethanolic extract was fractionated and detected by liquid chromatography. The antistaphylococcal effects of the plant formulations were studied in detail in vitro by various biological methods, including microdilution methods for minimum inhibitory concentration (MIC), the checkerboard titration technique for synergy assay, fluorescence measurements for membrane disruption experiments, autoinducer-2-mediated bioassay for quorum sensing inhibition, and counting of colony-forming units for relative adhesion. Morphology was examined by transmission electron microscopy.
    RESULTS: Total ethanolic extract and chloroform fraction showed MICs of 128 and 32 μg/mL, respectively. Diplacol, diplacone, and 3\'-O-methyl-5\'-hydroxydiplacone inhibited S. aureus growth in the range of 8-16 μg/mL. Synergistic potential was shown in combination with mupirocin and fusidic acid. The ethanolic extract and the chloroform fraction destroyed the cell membranes by 91.61% and 79.46%, respectively, while the pure compounds were less active. The ethanolic extract and the pure compounds reduced the number of adhered cells to 47.33-10.26% compared to the untreated control. All tested plant formulations, except diplacone, inhibited quorum sensing of S. aureus. Transmission electron microscopy showed deformation of S. aureus cells.
    CONCLUSIONS: The products from the fruit of P. tomentosa showed antimicrobial properties against S. aureus alone and in combination with antibiotics. By affecting intracellular targets, geranylated flavonoids proposed novel approaches in the control of staphylococcal infections.
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