纳米抗菌剂抗菌性能研究进展

纳米抗菌剂是新型高效的抗菌材料,使用安全、方便,稳定性好,抗菌谱广,抗菌效力强,已逐步应用于纺织、建筑、医疗等行业。我们分析了近几年对抗菌纳米粒子及其复合物的实验研究,简要综述纳米抗菌剂抗菌活性的研究成果,展望纳米抗菌剂发展的主要趋势,为制备更直接有效的纳米抗菌剂提供理论基础和实验研究依据。     

纳米酶的抗菌作用及其机制研究进展

抗生素类药物的发现和使用给人类提供了抗击细菌感染的强大武器。但是,抗生素长期使用导致的细菌耐药问题限制了其在临床上的应用。开发新型的基于纳米酶(Nano-Enzyme)的新型抗菌剂为解决上述问题提供了新思路。将纳米酶可以归为两大类:一类是酶和纳米材料的复合材料;另一类是纳米材料本身具有类酶活性。因为银(Ag)纳米粒子是历史最悠久且研究最广泛的纳米抗菌剂,而且其抗菌机制多样化,因此将Ag纳米粒子的抗菌机制和最新进展单独论述。纳米抗菌剂可以组合多种抗菌机制协同抗菌,从而提高其抗菌性能。因此,在这篇综述中系统介绍了Ag纳米粒子和上述2种类型纳米抗菌剂的最新研究进展和抗菌机制,重点介绍了纳米材料的物理性质对抗菌活性和生物安全性的影响。最后,该综述还强调了该领域目前面临的问题和挑战,并对该领域的发展前景进行了展望。     

硅纳米针阵列抗菌材料的制备及其抗菌性能研究

本文以简易经济的金属辅助化学刻蚀技术制备了具有高效杀菌性能的硅纳米抗菌材料并研究其形貌与结构,以大肠杆菌和金黄色葡萄球菌为代表菌株,研究了纳米针抗菌材料的抗菌活性。实验证明,该抗菌材料对在其表面培养3 h的大肠杆菌和金黄色葡萄球菌的杀菌效率分别为85.12%,76.40%,表明该材料对革兰氏阳性和革兰氏阴性菌均有高的杀菌效果,所制备的抗菌材料有望为医疗卫生系统在抵抗细菌污染方面提供解决方案。     

研究报告：抗肿瘤药物长循环高分子脂质体的研究

脂质体作为一种药物基因载体已得到广泛应用,然而其仍然具有物理化学稳定性差、易发生团聚、难以多功能化等缺点．通过使用合成的双亲性高分子共轭亚油酸修饰聚赖氨酸(PC)代替小分子磷脂制备的高分子脂质体(PLs),不仅保留了脂质体的优势,并且克服了上述缺点;通过对高分子进行聚乙二醇(PEG)修饰,可使制备的高分子脂质体具有长循环性．结果表明,高分子脂质体粒径为纳米级,具有药物缓释性能、较低的细胞毒性及较高的细胞内吞效率．     

金属纳米团簇的合成及抗菌效应的研究进展

金属纳米团簇(M NCs)是近年来出现的一类由几个至数百个原子组成的具有超小尺寸结构(<3 nm)的新型功能材料,因其有独特的物理化学性质以及良好的生物相容性,被广泛应用于生物分析、药物输送、医学成像以及肿瘤治疗等领域。最近,利用M NCs作为新型纳米抗菌材料解决细菌感染方面的研究成为热点,已经在抗生素耐药、致病菌的检测和治疗等方面得到了应用,为解决抗感染问题提供了新思路。本文首先介绍了不同M NCs的合成及性质的研究进展,然后根据近几年来国内外的相关研究,综述了单一M NCs及其复合物抗菌效应的应用现状及其作用机制,并对其作为一种新型纳米抗菌材料在实际应用过程中的稳定性、多功能性以及协同抗菌作用存在的问题进行了展望。     

β-环糊精主客体识别抗菌剂及抗菌性能研究进展

细菌污染与人类的生存息息相关,随着多重耐药细菌的增加,提高抗菌剂抗菌性能、抑制细菌传播和感染成为抗菌剂研究领域的热点问题。利用β-环糊精的包结作用与抗菌剂主客体识别改善抗菌剂的理化性质,增强抗菌剂的抗菌性能引起了广泛关注。环糊精具有内疏水外亲水的特殊结构,疏水内腔可选择性地与空腔大小相匹配的疏水客体分子进行主客体识别,将抗菌剂包合,从而改善抗菌剂理化性质,提高抗菌剂抗菌性能。本文综述了β-环糊精及其衍生物与有机抗菌剂、天然抗菌剂主客体识别对抗菌剂理化性质及抗菌性能的影响,分析了主客体识别的包合机理及主客体之间的作用,系统地归纳总结了环糊精主客体识别抗菌剂对不同细菌的抗菌作用及在医药、纺织、食品等领域的应用研究现状,以期为环糊精主客体识别抗菌剂的深入研究及应用提供参考。     

抗菌生物材料的研究进展

生物高分子材料(医用缝合线、导尿管等)及人工器官(心瓣膜、人工肾等)的应用日益广泛,使用过程中引发的细菌性感染导致诸多严重后果,不容忽视。基于感染机理,人们通过对生物材料表面进行不同的改性,如通过阻止细菌黏附达到抗菌效果、通过干扰细菌细胞的组成取得杀菌效果等,研究了不同的抗菌机理。本综述了新型有机高分子抗菌剂的发展,提出对生物相容性良好的聚氨酯、聚砜、聚醚砜等材料进行表面改性,使之具有好的抗菌能力,是未来抗菌生物材料的研究与发展方向。     

蒙脱土/还原氧化石墨烯负载纳米铜复合物的制备及其抗菌性能的研究

本文研究了蒙脱土/还原氧化石墨烯负载纳米铜(MMT-rGO-CuNPs)复合抗菌材料的制备及其抗菌性能。通过X射线衍射图谱的检测,确定MMT-rGO-CuNPs复合物已经成功。为了研究复合物的抗菌活性,通过观察大肠杆菌和金黄色葡萄球菌的表面形貌变化和细菌体外离子浓度变化,证明MMT-rGO-CuNPs复合物对金黄色葡萄球菌的抗菌性能要强于对大肠杆菌。     

铁载体-抗生素耦合物:一种新型的抗菌制剂

随着细菌对抗生素耐药性的增强,寻找一种新型抗菌制剂越来越重要。细菌细胞外膜对药物分子的通透性降低是引起致病菌产生耐药性的一个重要因素,克服膜介导耐药性的方法之一是利用铁载体-抗生素耦合物。铁载体是细菌分泌的一种小分子铁离子螯合物,与铁离子螯合后被特定的外膜受体识别并转运至胞浆内供细菌利用。人工合成的铁载体-抗生素耦合物被特定外膜受体识别后主动转运跨过外膜进入胞质内。当铁载体-抗生素耦合物到达细胞质,它们通过释放药物杀死微生物,这可以阻止进一步获取铁离子,并且耦合物自身也可以作为一种抗菌剂。本文综述了铁载体-抗生素耦合物作为一种新型抗菌制剂的研究进展,有助于为进一步研发新型抗菌药物提供理论基础,对治疗耐药性细菌性疾病具有潜在的重要意义。     

一种新型仿生抗菌剂的功能研究

抗菌剂α-炔丙基-γ-亚甲基-γ-丁内酯是以天然抗菌物质原白头翁素为基础,利用仿生技术合成出的新型抗菌剂.通过悬液杀菌法进行最小抑菌浓度测定、悬液定量法及活体菌落计数法进行最小杀菌浓度测定等生化试验对其抗菌效果进行了检验;通过细胞壁结构的完整性实验及透射电镜观察等理化实验对其抗菌机理做初步研究,为其应用于实践提供依据.抗菌剂α-炔丙基-γ-亚甲基-γ-丁内酯对大肠杆菌、金黄色葡萄球菌、白色念珠菌及马拉色菌均具有良好的抑菌作用,对马拉色菌的抑菌作用尤为突出,并对其具有良好的杀菌作用.其对马拉色菌的最小抑菌浓度为0.5mg/ml,当其浓度在10mg/ml时,对马拉色菌具有瞬杀作用(作用1min对球形马拉色菌的杀灭率可达到99.99％).通过胞壁完整性实验以及电镜观察实验表明该抗菌剂的抑菌机制并不是完全破坏胞壁结构,但是对细胞壁有一定影响.     

Nanocarriers for combating biofilms: Advantages and challenges

Bacterial biofilms are highly resistant to antibiotics and pose a great threat to human and animal health. The control and removal of bacterial biofilms have become an important topic in the field of bacterial infectious diseases. Nanocarriers show great anti-biofilm potential because of their small particle size and strong permeability. In this review, the advantages of nanocarriers for combating biofilms are analysed. Nanocarriers can act on all stages of bacterial biofilm formation and diffusion. They can improve the scavenging effect of biofilm by targeting biofilm, destroying extracellular polymeric substances and enhancing the biofilm permeability of antimicrobial substances. Nanocarriers can also improve the antibacterial ability of antimicrobial drugs against bacteria in biofilm by protecting the loaded drugs and controlling the release of antimicrobial substances. Additionally, we emphasize the challenges faced in using nanocarrier formulations and translating them from a preclinical level to a clinical setting.     

Studies on the antibacterial effects of negapillin in combination with other antibiotics and sulfa drugs

Summary The antibacterial effect of negapillin in combination with other antibiotics and sulfa drugs was studied using Gram+ve and Gram-ve bacteria as test organisms. Subsequently, various proportions of negapillin in combination with the antibiotics and the sulfa drugs were examined to determine the optimum proportions which exert maximum inhibitory effects on the bacterial growth. Mixtures of these antibiotics with negapillin were found more superior not only as antimicrobial agents but also for having comparatively low toxicity.     

A Novel Multifunctional Crosslinking PVA/CMCS Hydrogel Containing Cyclic Peptide Actinomycin X2 and PA@Fe with Excellent Antibacterial and Commendable Mechanical Properties

Bacterial infected environments and resulting bacterial infections have been threatening the human health globally. Due to increased bacterial resistance caused by improper and excessive use of antibiotics, antibacterial biomaterials are being developed as alternatives to antibiotics in some cases. Herein, an advanced multifunctional hydrogel with excellent antibacterial properties, enhanced mechanical properties, biocompatibility and self-healing performance, was designed through freezing-thawing method. This hydrogel network is composed of polyvinyl alcohol (PVA), carboxymethyl chitosan (CMCS), protocatechualdehyde (PA), ferric iron (Fe) and an antimicrobial cyclic peptide actinomycin X2 (Ac.X2). The double dynamic bonds among protocatechualdehyde (PA), ferric iron (Fe) and carboxymethyl chitosan containing coordinate bond (catechol-Fe) as well as dynamic Schiff base bonds and hydrogen bonds endowed the hydrogel with enhanced mechanical properties. Successful formation of hydrogel was confirmed through ATR-IR and XRD, and structural evaluation through SEM analysis, whereas mechanical properties were tested with electromechanical universal testing machine. The resulting PVA/CMCS/Ac.X2/PA@Fe (PCXPA) hydrogel has favorable biocompatibility and excellent broad-spectrum antimicrobial activity against both S. aureus (95.3 %) and E. coli (90.2 %) compared with free-soluble Ac.X2, which exhibited subpar performance against E. coli reported in our previous studies. This work provides a new insight on preparing multifunctional hydrogels containing antimicrobial peptides as antibacterial material.     

Novel histone-derived antimicrobial peptides use different antimicrobial mechanisms

The increase in multidrug resistant bacteria has sparked an interest in the development of novel antibiotics. Antimicrobial peptides that operate by crossing the cell membrane may also have the potential to deliver drugs to intracellular targets. Buforin 2 (BF2) is an antimicrobial peptide that shares sequence identity with a fragment of histone subunit H2A and whose bactericidal mechanism depends on membrane translocation and DNA binding. Previously, novel histone-derived antimicrobial peptides (HDAPs) were designed based on properties of BF2, and DesHDAP1 and DesHDAP3 showed significant antibacterial activity. In this study, their DNA binding, permeabilization, and translocation abilities were assessed independently and compared to antibacterial activity to determine whether they share a mechanism with BF2. To investigate the importance of proline in determining the peptides' mechanisms of action, proline to alanine mutants of the novel peptides were generated. DesHDAP1, which shows significant similarities to BF2 in terms of secondary structure, translocates effectively across lipid vesicle and bacterial membranes, while the DesHDAP1 proline mutant shows reduced translocation abilities and antimicrobial potency. In contrast, both DesHDAP3 and its proline mutant translocate poorly, though the DesHDAP3 proline mutant is more potent. Our findings suggest that a proline hinge can promote membrane translocation in some peptides, but that the extent of its effect on permeabilization depends on the peptide's amphipathic properties. Our results also highlight the different antimicrobial mechanisms exhibited by histone-derived peptides and suggest that histones may serve as a source of novel antimicrobial peptides with varied properties.     

酸枣果抗菌增敏活性成分的提取及生物学活性研究

采用不同极性的溶剂,从野生酸枣果和木枣果中由低极性到高极性依次提取获得不同极性范围的提取物,通过检测其抗菌作用和提取物与抗生素的协同抗菌作用,从中筛选具有抗菌增敏作用的活性提取物,并经活性追踪的柱层析分离纯化进一步得到活性精提物,通过GC-MS分析确定其组成成分,最后检测了该活性精提物的生物学活性。结果表明:(1)在所有的枣果提取物中仅酸枣果氯仿提取物具有广谱的抗菌作用,并能显著增强铜绿假单胞菌对氨苄青霉素的敏感性,而其他提取物均无相应的生物学活性。(2)由酸枣果氯仿提取物进一步精制得到的Fr.2a组分,经GC-MS初步分析显示它包含49.59%1,3-二氯丙醇、5.49%1,1-二氯甲醚、0.96%六氯乙烷、7.81%1,1,2,3-四氯-2-丙烯、1.33%月桂酸、1.34%十四酸、0.87%棕榈油酸、7.37%棕榈酸、9.75%邻苯二甲酸二丁酯、2.02%反式-13-十八碳烯酸、1.88%油酸酰胺、3.06%β-香树精、0.93%α-菖蒲醇、6.20%羽扇豆醇和1.42%乌索醛等成分。(3)酸枣活性提取物Fr.2a与多种抗生素联用显示出广泛的协同抗菌作用,同时Fr.2a呈剂量依赖性地促进微生物生物膜的形成,降低微生物的运动性和显著抑制牛奶中微生物的生长。该研究结果为酸枣果的药用产品和天然防腐剂的开发奠定了基础。     

Discovery of antimicrobial compounds targeting bacterial type FAD synthetases

The increase of bacterial strains resistant to most of the available antibiotics shows a need to explore novel antibacterial targets to discover antimicrobial drugs. Bifunctional bacterial FAD synthetases (FADSs) synthesise the flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These cofactors act in vital processes as part of flavoproteins, making FADS an essential enzyme. Bacterial FADSs are potential antibacterial targets because of differences to mammalian enzymes, particularly at the FAD producing site. We have optimised an activity-based high throughput screening assay targeting Corynebacterium ammoniagenes FADS (CaFADS) that identifies inhibitors of its different activities. We selected the three best high-performing inhibitors of the FMN:adenylyltransferase activity (FMNAT) and studied their inhibition mechanisms and binding properties. The specificity of the CaFADS hits was evaluated by studying also their effect on the Streptococcus pneumoniae FADS activities, envisaging differences that can be used to discover species-specific antibacterial drugs. The antimicrobial effect of these compounds was also evaluated on C. ammoniagenes, S. pneumoniae, and Mycobacterium tuberculosis cultures, finding hits with favourable antimicrobial properties.     

Triterpene sapogenin–polyarginine conjugates exhibit promising antibacterial activity against Gram-positive strains

Triterpene sapogenins are a group of biologically active compounds with antibacterial activity. However, the limited solubility and poor bioavailability of triterpene sapogenins restrict their therapeutic application. Polyarginine peptides are small cationic peptides with high affinities for multiple negatively charged cell membranes and possess moderate antibacterial activities. In this study, we designed and synthesized a series of sapogenin–polyarginine conjugates in which the triterpene sapogenin moiety was covalently appended to the positively charged polyarginine via click chemistry. A clear synergistic effect was found, and the conjugates exhibited potent and selective antibacterial activity against Gram-positive strains. Among them, BAc-R3 was the most promising compound, which was also proven to be nontoxic toward mammalian cells as well as stable in plasma. The mechanism of BAc-R3 primarily involves an interaction with the bacterial membrane, similar to that of antimicrobial peptides (AMPs). This scaffold design opens an avenue for the further development of novel antibiotics comprised of the combination of a peptide and a natural product.     

A novel copper (II) PAmPiCaT complex (cPAmPiCaTc) as a biologically potent candidate: A contraption evidence against methicillin-resistant Staphylococcus aureus (MRSA) and a molecular docking proof

Increasing in the alarm against the resistant bacteria due to the failure of antibiotics, thereby the need of more efficiency/potent molecule to treat infections. In the present investigation, series of piperazine derivatives 5(a-l) compounds were synthesized and they were characterised by different spectral techniques such as ¹H NMR, ¹³C NMR, IR and LCMS. A novel copper complex (cPAmPiCaTc) was developed for the first time by using potent analog 5e and characterized by IR and LCMS. The cPAmPiCaTc evaluated for antibacterial activity and showed excellent antimicrobial effect (12?±?0.08?mm, ZOI) at MIC 20?µg/mL against MRSA compared to standard antibiotics streptomycin and bacitracin at MIC 10?µg/mL. The results show promising anti-staphylococcal action against MRSA which confirmed by membrane damage, bioelectrochemistry, gene regulation (SarA and DHFR), and in silico molecular docking studies. Further, the cPAmPiCaTc also showed excellent blood compatibility and this result pave the way for interesting metallodrug therapeutics in future against MRSA infections.     

贮存年份对北艾和蕲艾精油成分与抑菌活性的影响研究

本文采用水蒸汽蒸馏法提取了贮存0、1、2年的北艾和蕲艾精油,采用GC-MS检测精油化学成分,选取10种常见细菌,检测了其抗菌谱和最小杀菌浓度。结果发现:0、1年份北艾精油中小分子挥发性物质较多,随着贮存年份的增加,大分子挥发性物质随之增加;侧柏酮为蕲艾的特有成分。0年份艾叶精油的抑菌活性较高,对沙门菌、枯草芽孢杆菌、沙门菌耐药菌、绿脓杆菌均具有抑制作用。综上,不同贮存年份和品种的艾叶精油在化学成分、抗菌谱和抑菌活性方面均存在差异,综合考虑精油含量和抑菌活性,以0年份的北艾为原料提取精油最佳。     

抗菌肽活性及天然抗菌肽的改造

抗菌肽具有抗菌谱广、热稳定性强、分子量小及免疫原性小等特点,其杀菌机制独特,病原菌不易产生耐药性,有望开发成新一代肽类抗生素。本文主要综述了影响抗菌肽生物活性的生化性质,即螺旋度、疏水性、两亲性、正电荷数等,并从结构的角度论述了其对抗菌肽抑菌活性的影响。部分抗菌肽具有空间结构不稳定、溶血活性等缺点,限制了其临床应用。因此,对天然抗菌肽的改造也成为目前抗菌肽的研究热点,本文还综述了天然抗菌肽的改造方法。