The interaction of nanostructured antimicrobials with biological systems:Cellular uptake,trafficking and potential toxicity

Nanomaterials have been found increasing applications in the food sector.Nanostructured antimicrobials can be incorporated either to food matrix of food packaging or to provide extended safety and quality.However,the interactions and effects of nanomaterials with biological systems are still poorly understood.Nanoparticles can enter the organism by oral,dermal and inhalation routes and distributed to different tissues by the circulatory system.Increasing evidence indicate that targeting to specific tissues,cellular uptake and intracellular fate of nanoparticles are strongly influenced by size,shape and surface properties.The specific characteristics of nanomaterials are also determinant for their toxicity in higher organisms.The dose,exposure time and administration route are important aspects influencing toxicity of nanoparticles as well.Both in vitro and in vivo evaluation studies on different types of nanostructures have providing information to support a better understanding about the interactions of nanoscale materials with biological systems.

Review on Zinc Oxide Nanoparticles: Antibacterial Activity and Toxicity Mechanism

Antibacterial activity of zinc oxide nanoparticles(Zn O-NPs) has received significant interest worldwide particularly by the implementation of nanotechnology to synthesize particles in the nanometer region. Many microorganisms exist in the range from hundreds of nanometers to tens of micrometers. Zn O-NPs exhibit attractive antibacterial properties due to increased specific surface area as the reduced particle size leading to enhanced particle surface reactivity. Zn O is a bio-safe material that possesses photo-oxidizing and photocatalysis impacts on chemical and biological species. This review covered Zn O-NPs antibacterial activity including testing methods, impact of UV illumination, Zn O particle properties(size, concentration, morphology, and defects), particle surface modification, and minimum inhibitory concentration. Particular emphasize was given to bactericidal and bacteriostatic mechanisms with focus on generation of reactive oxygen species(ROS) including hydrogen peroxide(H2O2), OH-(hydroxyl radicals), and O2-2(peroxide). ROS has been a major factor for several mechanisms including cell wall damage due to Zn O-localized interaction, enhanced membrane permeability, internalization of NPs due to loss of proton motive force and uptake of toxic dissolved zinc ions.These have led to mitochondria weakness, intracellular outflow, and release in gene expression of oxidative stress which caused eventual cell growth inhibition and cell death. In some cases, enhanced antibacterial activity can be attributed to surface defects on Zn O abrasive surface texture. One functional application of the Zn O antibacterial bioactivity was discussed in food packaging industry where Zn O-NPs are used as an antibacterial agent toward foodborne diseases. Proper incorporation of Zn O-NPs into packaging materials can cause interaction with foodborne pathogens, thereby releasing NPs onto food surface where they come in contact with bad bacteria and cause the bacterial death and/or inhibition.

Antimicrobial peptides: mechanism of action, activity and clinical potential

The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria.As an excellent candidate to overcome antibiotic resistance,antimicrobial peptides(AMPs)that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity.These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action.This comprehensive review provides a broad overview of AMPs from the origin,structural characteristics,mechanisms of action,biological activities to clinical applications.We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.

Chemical analysis and in vitro antimicrobial effects and mechanism of action of Trachyspermum copticum essential oil against Escherichia coli

Objective: To find a natural plant essential oil (EO) with excellent antimicrobial effect on food-borne bacteria and to explore the mechanism of its antimicrobial function against Escherichia colt (E. cal). Methods: The antimicrobial activity of seven EOs against Gramnegative E. coli ATCC 8739 and Gram-positive Staphylococcus aureus ATCC 6538 was investigated using agar disk diffusion method, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of each EO was determined using the broth dilution method. The chemical composition of the Trachyspermum copticum (T. copticum) EO was analyzed using gas chromatography mass spectrometry (GC/MS). In order to explore the mechanism of the antimicrobial action, 1 MIC and 2 MIC of T. copticum. EO was added to a suspension of E. coli, the growth curve and the scanning electron microscopy (SEM) analysis of E. coli, and the release of cell constituents and protein and potassium ions from the bacterial cell were measured. Results: The T. optician EO had the best antimicrobial activity against the test bacteria, and 10 compounds accounting for 94.57% of the total oil were identified, with the major components being thymol (46.22%), p-cymene (19.03%), and y-terpinene (22.41%). The addition of I MIC T. copticum. EO significantly inhibited the growth of E. coli and increased the release of cell constituents and protein and potassium ions from the bacterial cells. Scanning electron micrographs showed that T. copticum EO caused most of the E. co/i cell membranes to collapse and rupture, leading to cell death. Conclusions: These results indicate that T. copticum EO is a good natural antimicrobial agent for food-borne pathogens.

Assessment of flavonoid-rich extracts from dark peels of Ficus carica L.fruits for cosmeceutical and antimicrobial applications

Background:Exploring natural sources to identify new active ingredients for cosmeceutical and pharmaceutical applications is of interest to many researchers.Methods:Flavonoid-rich extracts from dark Ficus carica peels were investigated in the present study.Extracts were prepared from the peels of four dark cultivars(Bakor Noir,Bouankik,Azenjer and Tazegaght)using acidified methanol.The antimicrobial activity of the extracts was evaluated by the agar well diffusion assay followed by the minimal inhibitory concentration determination using the microdilution method against Gram-positive and Gram-negative pathogenic bacteria and two fungi.Cosmeceutical properties were evaluated by measuring antioxidant activity,ultraviolet absorption characteristics and sun protection factor values.The antioxidant activity of the extracts was measured using aβ-carotene-linoleic acid system.The toxicity of the extracts was assessed using a brine shrimp lethality assay.Results:The extracts contained high amounts of phenolic compounds(3.85–8.63 g/100 g),mainly flavonoids(up to 5 g/100 g).Multiple antibacterial activities were recorded against Gram-positive and Gram-negative bacteria,with the best actions against Bacillus subtilis(minimal inhibitory concentration=156.25µg/mL),Staphylococcus aureus and Pseudomonas aeruginosa(minimal inhibitory concentration=312.5µg/mL),but no antifungal activity was recorded.Azenjer extract showed high inhibition of lipid oxidation evaluated by theβ-carotene bleaching assay with a half-maximal inhibitory concentration of 88.84µg/mL.All extracts showed absorption peaks in the ultraviolet range and Azenjer and Tazegaght extracts at 25 mg/mL presented sun protection factor values>15.The brine shrimp toxicity assay results revealed lethal concentration of 50%values greater than 2,000µg/mL,indicating the safety of the extracts.Conclusion:Therefore,Ficus carica peel extracts could be considered original ingredients with potential applications in the formulation of antibacterial drugs and skincare products.

Conjugation with Acridines Turns Nuclear Localization Sequence into Highly Active Antimicrobial Peptide

The emergence of multidrug-resistant bacteria creates an urgent need for alternative antibiotics with new mechanisms of action. In this study, we synthesized a novel type of antimicrobial agent, Ac r_3-NLS, by conjugating hydrophobic acridines to the N-terminus of a nuclear localization sequence(NLS), a short cationic peptide. To further improve the antimicrobial activity of our agent, dimeric(Acr_3-NLS)_2 was simultaneously synthesized by joining two monomeric Acr_3-NLS together via a disulfide linker. Our results show that Acr_3-NLS and especially(Acr_3-NLS)_2 display signifi cant antimicrobial activity against gramnegative and gram-positive bacteria compared to that of the NLS. Subsequently, the results derived from the study on the mechanism of action demonstrate that Acr_3-NLS and(Acr_3-NLS)_2 can kill bacteria by membrane disruption and DNA binding. The double targets—cell membrane and intracellular DNA—will reduce the risk of bacteria developing resistance to Acr_3-NLS and(Acr_3-NLS)_2. Overall, this study provides a novel strategy to design highly eff ective antimicrobial agents with a dual mode of action for infection treatment.

Evaluation of the Antimicrobial Effect of <i>Nepeta cataria</i>and <i>Basella alba</i>against Clinically Resistant <i>Acinetobacter baumannii</i>in Nairobi, Kenya

Acinetobacter baumannii is among the common nosocomial infections microorganisms in the Intensive Care Unit (ICU). Antimicrobial resistance (AMR) is one of the major significant concerns in developing nations due to either over-use or inadequate use of antimicrobial agents. The purpose of this study was to emphasize the potential antimicrobial activity of Nepeta cataria and Basella alba against nosocomial diseases caused by Acinetobacter baumannii. Nepeta cataria and Basella alba leaves were collected from Oldonyo Sabuk National Park and Botanical garden JKUAT respectively. The leaves were dried under shade at room temperature for thirty days. After methanolic and aqueous plant extraction, the percentage yield was determined, and the extracts were subjected to toxicity testing using brine shrimp eggs and preliminary phytochemical screening. The results recorded from this study demonstrated that 70% methanolic extract of Nepeta cataria and Basella alba had greater antimicrobial effect against Acinetobacter baumannii than aqueous extracts. Nepeta cataria extracts showed greater antimicrobial effect than Basella alba extracts. The methanolic plant extracts had MIC values 60 mg/ml when tested against Acinetobacter baumannii. The phytochemical screening showed the presence of various phytochemical constituents from the methanolic and aqueous extraction of Nepeta cataria and Basella alba. The methanolic plant extracts revealed more phytochemicals as compared to aqueous extracts. More phytochemicals were detected from Nepeta cataria than Basella alba plant extracts.

吗啉硝唑临床应用的研究进展

从结构特点、抗菌机制、抗菌活性、药动学、药物相互作用及临床应用等方面全面介绍吗啉硝唑的研究进展,为深入研究提供参考。吗啉硝唑作为新型硝基咪唑类抗菌药,抗菌活性强,不易产生耐药性,临床应用日益增多。多项研究证实吗啉硝唑疗效显著,安全性高。吗啉硝唑具有科研和临床应用价值,值得深入研究。

卤化合成α螺旋抗菌肽Cl-FR18的抑菌活性、安全性及稳定性研究

为了对α螺旋抗菌肽FR18进行卤化并了解卤化抗菌肽Cl-FR18的功能特性,对α螺旋抗菌肽FR18的N端第1个苯丙氨酸进行氯代,得到合成肽Cl-FR18,并进行抗菌活性、溶血活性、细胞毒性及稳定性检测。结果显示:Cl-FR18对7株指示菌均有良好的抑菌活性,其中对大肠杆菌K88和鲍曼不动杆菌js1的最小抑菌浓度(MIC)为4μg/mL,高于未修饰肽FR18;Cl-FR18的溶血活性明显低于蜂毒肽和未修饰肽,在浓度为16μg/mL时仅引起221%的羊红细胞溶血。Cl-FR18保留了未修饰肽FR18较好的细胞选择性和安全性的特点,经Cl-FR18作用12 h后的细胞存活率均在90%以上,且Cl-FR18在不同的盐离子、蛋白酶溶液和温度环境中表现出一定的敏感性,MIC增至2~8倍。结果表明,经卤化后的抗菌肽Cl-FR18抑菌谱广,抑菌活性明显,且具有良好的安全性,其卤化合成策略为优化抗菌肽的改造方法提供了理论参考。

海藻基纳米银研究进展

病原菌对抗生素多重耐药性的增加而引发的持续感染、高医疗成本使公共卫生领域面临着巨大挑战。新型海藻基纳米银(Silver nanoparticles,AgNPs)抗菌剂的开发研究对病原菌的控制意义重大。文章对海藻基AgNPs的生物合成、表征方法、抗菌活性进行了综述,强调了海藻基AgNPs抗菌活性可能的作用机制,并对其未来的研究方向进行展望,旨在为海藻基AgNPs抗菌新材料的深度开发与应用提供研究思路和方向。

壳聚糖-金属氧化物复合抗菌材料研究进展

介绍了微生物类型、壳聚糖自身以及环境因素对壳聚糖抗菌性能的影响,总结了壳聚糖的抗菌机理,综述了近期壳聚糖与氧化铜、氧化锌和二氧化钛等金属氧化物复合抗菌材料的研究成果,展示了部分壳聚糖-金属氧化物复合抗菌材料在食品包装及生物医疗塑料方面的应用,最后分析并展望了该类复合抗菌材料研究的不足以及进一步的发展趋势。指出壳聚糖-金属氧化物复合抗菌材料的抗菌机理有待深入研究,后续将不断开发绿色友好的制备工艺,根据应用性场景针对性设计高效抗菌材料。

葡萄籽提取物和岩藻多糖组合物抗幽门螺杆菌作用及机制研究

该研究旨在探索葡萄籽提取物和岩藻多糖组合物体外抗幽门螺杆菌及其机制。该实验在体外培养幽门标准菌株ATCC 700392,采用微量肉汤稀释法测定组合物的最小抑菌浓度(minimum inhibitory concentration,MIC)及时间-抑菌曲线;采用实时荧光定量(real-time fluorescence quantitative PCR,RT-qPCR)方法测定组合物对脲酶相关ureB、ureI、鞭毛相关flaB、flgK、黏附相关alpA、babA、毒力相关VacA基因表达水平的影响;采用扫描电镜观察组合物对菌体形态的影响。结果显示,组合物对幽门标准菌株ATCC 700392具有一定的体外抗菌活性,其MIC为1.5 g/L。在抑制动力学中,组合物在0.375 g/L时,ATCC 700392菌株的生长开始受到抑制,抑制活性呈现剂量依赖,浓度越大则抑制效果越明显,当组合物质量浓度为1.5 g/L时可完全抑制幽门螺杆菌的生长。RT-qPCR检测结果显示,组合物可显著抑制脲酶相关ureI、鞭毛相关flaB、flgK、黏附相关alpA、babA、毒力相关VacA基因等的表达。此外,扫描电镜观察到经组合物处理的菌体表面出现破损、菌体凹陷萎缩等明显的形态破损特征。该研究结果表明葡萄籽和岩藻多糖组合物在体外对幽门螺杆菌标准菌株有明显的抑制活性,其作用机制可能是通过抑制脲酶、抑制鞭毛相关的运动能力、抗黏附、破坏细菌形态等起到抑制幽门螺杆菌定殖的作用。该研究为更好地开发和利用葡萄籽岩藻多糖组合物提供了良好的科学实验支撑。

金属类化合物在抗菌领域的应用现状及展望

金属有机络合物具有悠久的临床应用历史,在治疗高血压、皮肤感染和胃肠道疾病方面表现出显著效果。随着近年来研究的进展,金属类化合物在抗细菌感染治疗中的应用及其作用机制受到了广泛地研究。笔者以3种常用金属类化合物为例,综述了金属类化合物在抗菌领域的研究进展、作用机制,并阐述了新型含金属药物以及中药提取成分及其衍生物金属络合物的研究动态,分析了金属药物在抗菌领域的潜在优势。

阿米巴穿孔素A的活性机制及其作为天然抗菌蛋白的潜在应用

当今,抗生素耐药性已成为全球面临的严峻挑战,导致传统抗生素的疗效受到限制。抗菌蛋白是一类多样的天然抗菌分子,广泛分布于动植物和微生物中,通过与细菌相互作用破坏其完整性,从而实现杀菌作用。与传统抗生素相比,抗菌蛋白还具有增强宿主免疫响应、降低细菌耐药风险等优势。阿米巴穿孔素A(Amoebapore A,APA)是一种由阿米巴原虫分泌的古老天然抗菌蛋白,通过增加细菌细胞膜的通透性和破坏细胞结构展现广谱杀菌活性。对APA的活性机制进行概述,旨在为开发以天然抗菌蛋白为基础的新型抗生素提供理论基础,以更好地解决抗生素耐药问题。

Comparative Study of the Biological Activities of the Skin Secretions from Six Common Chinese Amphibians

Water soluble skin secretions of six common Chinese amphibians were studied for their biological and enzymatic activities.The skin secretions of Tylototriton verrucosus,Bombina maxima ,and Bufo andrewsi were found toxic to mice with the intraperitoneal LD 50 of 11 5?mg/kg,18 8?mg/kg,and 264?mg/kg,respectively.No acute lethal toxicities were observed for the skin secretions of Rana nigromaculata,Rana guentheri and Rana limnocharis in a dose up to 500?mg/kg.The lethal toxicities of the skin secretions of T verrucosus and B maxima to mice are in the same grade as those of Viperidae snake venoms.The toxic components in T verrucosus and B maxima skin secretions are the proteins with molecular weights ranging from 3 to 60?kDa.All the skin secretions had both proteolytic activity and trypsin inhibitory activity.The skin secretions from T verrucosus , B maxima and B andrewsi also displayed wide spectrum antimicrobial activity.On the other hand,the skin secretions from B andrewsi and B maxima showed cytotoxicity on human cancer cells.All the six samples had not significant effects on mammalian blood coagulation system.Phospholipase A 2 activity was only found in the skin secretions of T verrucosus .None of these skin secretions showed acetylcholine esterase activity.

家蝇抗菌肽抗菌活性及抗菌机制的初步研究

目的 研究家蝇抗菌肽的抗菌活性及抗菌机制。方法 用损伤感染的方法诱导家蝇幼虫表达抗菌肽 ,通过 Sephadex过滤层析和 HL PC技术纯化提取 ,用平板法和稀释法作抗菌活性试验 ,并用电子扫描技术研究抗菌肽的抗菌机制。结果 家蝇抗菌肽对铜绿假单胞菌、大肠埃希氏菌、耐甲氧西林金黄色葡萄球菌( MRSA)均有明显的抗菌活性。大肠埃希氏菌与 5 0 μg/ml的纯化抗菌肽溶液一起 37℃孵育 6 0 min后 ,大肠埃希氏菌不能存活。经电镜扫描观察发现 ,细菌的细胞膜出现破损和穿孔现象。结论 家蝇抗菌肽具有明显的广谱抗菌活性 ,对阴性杆菌和阳性球菌均有杀伤作用。

山苍子油的抑菌活性及机理研究

采用抑菌圈实验和试管二倍稀释法对山苍子油的抑菌活性、最低抑菌浓度(MIC)进行测定,研究了山苍子油对食品中常见的黑曲霉、大肠杆菌、金黄色葡萄球菌和枯草芽孢杆菌的抑菌机理。结果表明:山苍子油对4种受试菌的抑制效果差异较大,对黑曲霉的抑制作用很强(MIC值0.11μL/mL),对金黄色葡萄球菌、枯草芽孢杆菌的抑制作用较弱(MIC值均为0.47μL/mL);山苍子油对温度具有良好的稳定性,121℃,10min加热处理对精油的抑菌效果无明显影响;经山苍子油处理一段时间后的蛋白质利用率有所下降,细菌通透性明显增强,引起内含物渗漏。结果表明,山苍子油的抑菌机制可能在于破坏细菌细胞膜结构,导致细菌细胞变形和菌体蛋白质减少,直至菌体分解为碎片。

鱼精蛋白——一种新型的食品防腐剂

鱼精蛋白是一种存在于各类动物精巢组织中的多聚阳离子肽,也是一种高效、安全、值得开发的新型 食品天然防腐剂。本文对鱼精蛋白的组成、提取工艺、抗菌特性、抗菌机理、毒性以及存在的问题和展望等方面 进行了简述。

鱼精蛋白抑菌机理及在食品防腐中的应用

鱼精蛋白是一类天然的阳离子抗菌肽,具有广谱抑菌活性。鱼精蛋白主要是通过破坏细菌的细胞壁、细胞膜及改变细胞的渗透性等途径抑制甚至杀死细菌细胞。在鱼精蛋白抑制细菌的同时,细菌也产生多种机制对抗鱼精蛋白。温度、pH、阳离子和EDTA等多种理化因子影响鱼精蛋白对细菌的抑制效果。由于鱼精蛋白在抑菌防腐方面的众多优势,目前已成为非常有发展前景的食品防腐剂。

黄酮化合物抗菌机理的研究进展

抗生素耐药是一个重大的全球性问题,迫切需要开发新的抗菌治疗药物。黄酮是植物源化合物,具有潜在的抗菌活性,其可能作用机制为直接的抑菌作用,与抗生素的协同作用,抑制细菌的毒力因子,如群体感应信号受体、酶和毒素,在细胞水平上抑制细菌生物膜的形成,抑制细菌粘附到宿主受体,中和细胞毒作用。本文介绍了近几年来黄酮化合物抗菌机理的最新进展,为天然抗菌药物的开发提供理论依据。