新型抗菌剂——群体感应抑制剂与传统抗菌剂对大肠杆菌的联合毒性效应

群体感应抑制剂(QSIs)作为一种抗生素的可能代替品,具有广阔的应用前景.一些研究指出QSIs与传统抗菌药物联合使用可以在提高药效的同时降低细菌耐药性.随着QSIs使用量地逐渐增大,在环境中可能与传统抗菌剂以混合的形式存在,因此有必要研究QSIs与传统抗菌剂的潜在联合毒性效应.但是,在目前的相关联合毒性效应研究中,被研究的传统抗菌剂种类有限,传统抗菌剂与QSIs的联合毒性效应可能由于传统抗菌剂的不同而发生改变.本文以大肠杆菌为受试生物,以磺胺和银类抗菌剂作为传统抗菌剂的代表,研究了两类传统抗菌剂与QSIs的二元以及三元联合毒性效应.结果表明,在磺胺-QSIs的30组二元联合毒性效应中,有24组表现为拮抗,6组表现为相加;在银类抗菌剂-QSIs的10组二元联合毒性效应中,有6组表现为拮抗,4组表现为相加;在磺胺-银类抗菌剂-QSIs的60组三元联合毒性效应中,有47组表现为拮抗,13组表现为相加.通过对比2种银类抗菌剂与QSIs的二元联合毒性效应,可以看出2种银类抗菌剂提供制毒部分的可能均为银离子;并且由于银类抗菌剂能最快地进入细菌细胞并完成与巯基的结合进而发挥药效,所以在三元混合中,银类抗菌剂可能起主要作用.     

中药抗菌剂对费氏弧菌的单一及联合毒性效应

抗生素滥用所导致的环境问题日益受到人们的关注,寻找传统抗生素的可能替代品迫在眉睫.从中药中提取的具有抗菌活性的化合物(简称中药抗菌剂)因具有资源丰富、抗菌谱广和不良反应低等特点,有望成为未来替代抗生素的关键.因此,有必要探究中药抗菌剂的毒性效应,这可以对未来中药抗菌剂使用后的生态风险提供指导.本文以费氏弧菌作为模式生物,分别测定了大黄素(emodin,EMO)、大黄酸(rhein,RH)、芦荟大黄素(aloe-emodin,AE)和双氢青蒿素(dihydroartemisinin,DHA)4种中药抗菌剂对费氏弧菌的单一和多元联合毒性,同时进行了抑菌作用机理的初步讨论.结果 表明,4种中药抗菌剂对费氏弧菌的生物荧光均能产生较为明显的抑制作用,毒性排序是EMO＞RH＞AE＞DHA.而当EMO、RH、AE和DHA混合暴露时,混合物在高浓度区间的联合毒性作用模式均为拮抗,推测是受试中药抗菌剂之间互相竞争性地对NADH脱氢酶产生抑制作用,从而导致对发光反应的抑制作用较单一暴露时减弱.本研究对未来中药抗菌剂单一及联合毒性效应的研究具有积极的推动作用,有望为今后中药抗菌剂的生态风险评价提供参考.     

纳米银复合材料与抗生素的联合抗菌性能及相关机制研究

抗生素的滥用导致细菌耐药问题日益严重,人类迫切需要开发出新的抗菌药物以减少细菌耐药问题。基于纳米银制备而成的纳米银复合材料在兼顾纳米银抗菌性能的同时不仅能够克服单一纳米银释放速度快、不稳定等缺点,还能缓解细菌耐药的问题,因此被认为是一类具有广泛应用前景的新型抗菌剂。已有研究表明,单一纳米银与某些抗生素的联合使用可以达到协同抗菌效果,但目前尚缺乏对纳米银复合材料与抗生素的联合抗菌性能及机制的研究。本文首先制备出3种不同结构的纳米银复合材料,包括二氧化硅-聚多巴胺-纳米银复合材料(SiO_2-PD-AgNPs)、纳米银@二氧化硅复合材料(AgNPs@SiO_2)和纳米银@二氧化硅-聚多巴胺-纳米银复合材料(AgNPs@SiO_2-PD-AgNPs)。随后测定了纳米银复合材料对大肠杆菌(Escherichia coli, E. coli)和枯草芽孢杆菌(Bacillus subtilis, B. subtilis)的单一毒性效应。结果显示,AgNPs@SiO_2-PD-AgNPs复合材料对2种菌的单一毒性均大于其余2种纳米银复合材料。因此,笔者以AgNPs@SiO_2-PD-AgNPs作为代表,测定了纳米银复合材料与硫酸卡那霉素(kanamycin sulfate, KS)/盐酸土霉素(oxytetracycline hydrochloride, OH)的二元联合抗菌性能,发现AgNPs@SiO_2-PD-AgNPs与KS联合可以对E. coli产生协同效应。协同效应产生的主要原因可能是:AgNPs@SiO_2-PD-AgNPs释放出的纳米银会和KS发生键合反应生成KS-纳米银复合物,导致纳米银释放出大量的Ag+增加了细胞膜的通透性,从而使得进入细菌内的Ag~+和KS比单独作用时进入胞内的抗菌剂增多,产生更强的抗菌性能,从而表现出协同抗菌效应。本研究基于新型纳米银复合材料与抗生素的联合抗菌性能实验探究了纳米银复合材料与特定抗生素联合用药的最佳组合和相关机制,为今后开发新型抗菌材料提供了新思路并为相关联合用药提供参考。     

链霉菌S227抗耐药性物质的分离及其活性研究

在抗耐药性活性筛选过程中,发现分离自四川峨嵋山森林土壤的一株链霉菌S227(Streptomyces sp.)的发酵液具有抗细菌抗生素耐药性生物活性.利用已建立的抗耐药性的活性检测方法(专利号:ZL01128969.4)[1]为跟踪手段,采用有机溶剂萃取、硅胶柱层析以及薄层层析等方法,对该菌发酵液中抗耐药性活性物质进行分离纯化,得到了具有抗耐药性的活性单体S227-4,初步鉴定为四聚糖.利用MIC法对该样品的抗耐药活性进行研究:在证明该样品本身不具有抗菌活性的基础上,以临床分离的耐药菌株为指示菌,考察了该样品与抗生素联合使用时对耐药菌抗生素MIC(最小抑菌浓度)值的影响,结果表明,S227-4在不影响耐药菌生长的浓度下与不同的抗生素联合使用,可以明显提高不同耐药菌对不同抗生素的敏感性,如S227-4(200μg/mL)可以使S.aureus12334对红霉素的敏感性提高128倍.图2表2参8     

氧氟沙星对斜生栅藻的毒性效应

氧氟沙星(ofloxacin,OFLX)又名氟嗪酸,是第三代喹诺酮类抗生素.由于其具有抗菌谱广、抗菌活性强的特点,且与其它抗菌药物无交叉耐药性,已被广泛应用于畜禽疾病防治和水产养殖中.进入环境的抗生素不仅会对靶生物起作用,也可能会对非靶生物和生态系统产生影响.藻类是水生生态系统的初级生产者,是评价水环境质量的重要指标.斜生棚藻作为国际经济合作和发展组织(OECD)制定的藻类生长抑制试验的标准藻种,具有对毒物敏感、繁殖快、易分离培养等特点.     

水产养殖环境中抗生素抗性基因（ARGs）的研究及进展(Research Advancement of Antibiotics Resistance Genes（ARGs）in Aquaculture Environment)

抗生素在现阶段的水产养殖中具有不可替代的作用,但长期滥用抗生素会诱导水生动物体内产生携带抗性基因(ARGs)的细菌株,尤其是多重耐药性菌株的产生将使得各种疾病的治疗更加棘手.抗性基因一旦被排泄到水产环境中不仅会对养殖区域和周围的环境造成潜在的基因污染,而且还会通过各种可移动遗传元件如质粒、转座子、整合子等的水平迁移作用进入其他致病菌和环境细菌中,对人类的健康安全构成潜在的威胁.论文对抗生素抗性基因在水产养殖业中的来源、污染现状、潜在的传播途径和相关的检测方法进行了综述,指出了开展水产养殖业中抗生素抗性基因污染研究的必要性,建议政府和有关部门尽快进行水产养殖业抗生素抗性基因的污染机理与控制对策研究.     

传粉蜜蜂介导的细菌耐药性传播及其生态与健康风险

目前,抗菌药物的滥用造成了临床和环境中普遍存在的细菌耐药性问题,而细菌耐药性在环境中不断富集和传播扩散会通过食物网对生态安全及人体健康构成威胁。蜜蜂作为最重要的传粉昆虫,在世界各地广泛分布。然而,蜜蜂近年来频繁暴露于抗生素、杀虫剂和杀螨剂等药物,而野外杀虫剂的大量使用被认为是导致世界各地蜜蜂种群数量下降的关键因素。蜜蜂传花授粉的生物学特性使得蜂群与周围环境之间发生频繁的交流,可能导致蜜蜂传粉过程中蜂群与周围环境的交叉污染并发生细菌耐药性的传递。因此,蜜蜂可能成为生态系统中细菌耐药性传播的潜在“帮凶”。传粉蜜蜂介导下的细菌耐药性传播也将对蜂群健康、食品安全乃至生态系统安全构成威胁。本文综合国内外相关研究进展,系统分析了环境污染物暴露对蜜蜂以及蜜蜂肠道耐药基因组的潜在影响,并详细阐述了传粉蜜蜂介导下的细菌耐药性的传播,总结了蜜蜂主要通过蜜蜂-蜜蜂、蜜蜂-植物以及蜜蜂-环境的途径促进细菌耐药性的传播。最后,探讨了蜜蜂介导的细菌耐药性传播对蜂群健康、生态环境以及人体健康的潜在影响。     

免模板法合成高纯介孔氧化镁纳米抗菌剂

通过尿素和四水合乙酸镁的水热沉淀反应合成了多孔碳酸镁纳米带,再经高温煅烧制备了高纯度介孔氧化镁纳米颗粒.对所得材料进行了结构性质的表征,并利用最小抑菌浓度试验、抑菌圈试验、和摇瓶灭活试验考察了该材料对常见致病菌的抗菌活性.结果表明,该材料平均粒径为50 nm,含有许多直径约为3 nm的介孔,比表面积可达193.7 m~2·g~(-1),并赋予材料大量的缺陷位点和较高的抗菌活性,500 mg·L~(-1)的材料在24 h内对大肠杆菌和金黄色葡萄球菌可达到99.9%的杀菌百分率.此外,X射线晶体衍射、元素组成分析和X射线光电子能谱分析证实,以尿素和乙酸镁为前体,可以获得高纯度纳米氧化镁材料.     

长期有机无机肥配合施用土壤中添加不同肥料养分后土壤微生物短期变化

为了阐明改变肥料养分投入后土壤微生物特性的短期变化,采集长期定位有机无机肥配施的红壤水稻土,通过室内培育试验,观测添加不同肥料养分后土壤微生物生物量碳及BIOLOG群落功能多样性的变化.结果表明,长期有机无机肥配施土壤中添加无机肥料养分短期内( 185 d)降低了15％～22％的微生物生物量碳含量和55.6％的微生物群落平均光密度；添加有机肥料养分短期内提高了8％～42％的微生物生物量碳含量和992％的微生物群落平均光密度；而不添加肥料养分短期内提高了501％的微生物群落平均光密度,降低了微生物群落均一性,但对微生物生物量碳含量影响不大.此外,添加不同肥料养分均改变了土壤微生物群落碳源代谢模式.长期配施有机无机肥土壤中添加不同肥料养分后土壤微生物生态特征发生明显变化,其差异体现在微生物生物量碳与微生物碳源利用特性的变化上.     

长期不同施肥措施对红壤水稻土有机碳和养分含量的影响

将红壤丘陵地区的荒地开垦为水田不仅可以防治土壤侵蚀,而且能增加土壤肥力,提高农田生产力.本文研究了红壤荒地垦殖为稻田,长期定位施肥15年后不同施肥措施下水稻土的有机碳和养分含量特征.结果表明:不同施肥措施包括不施肥条件下,15年水稻垦殖都提高了土壤肥力.不同施肥措施水稻土的pH提高了0.9～1.3个单位.耕层土壤有机碳含龟达到8.19～1O.13 g·kg-1,全氮含量达到0.89～1.20 g·kg-1,有机碳与全氮含最都有明显提高,且有机碳和全氮含量之间相关性极显著.水稻土耕层全磷含量在0.25～0360 g·kg-1之间,有效磷含量在2.2～20.9 mg·kg-1之间,化学磷肥的培肥效果好于有机肥(猪粪),有机无机磷肥配施能显著提高土壤全磷和有效磷库.土壤全钾还未有明显变化,土壤速效钾含量在40.4～142.5 mg·kg-1之间,不同施肥措施除氮钾肥处理外都造成了土壤速效钾含量下降,秸秆还田到目前为止对于土壤速效钾含量还没有明显作用.     

Evaluation of 1,4-naphthoquinone derivatives as antibacterial agents: activity and mechanistic studies

● All 1,4-naphthoquinone hybrids exhibited significant antimicrobial activity. ● Presence of a hydroxyl group on aromatic B-ring of juglone was crucial for activity. ● Juglone can cause DNA damage by producing ROS and downregulation of RecA. ● Juglone has the potential to become a disinfectant. The diverse and large-scale application of disinfectants posed potential health risks and caused ecological damage during the 2019-nCoV pandemic, thereby increasing the demands for the development of disinfectants based on natural products, with low health risks and low aquatic toxicity. In the present study, a few natural naphthoquinones and their derivatives bearing the 1,4-naphthoquinone skeleton were synthesized, and their antibacterial activity against selected bacterial strains was evaluated. In vitro antibacterial activities of the compounds were investigated against Escherichia coli and Staphylococcus aureus. Under the minimum inhibitory concentration (MIC) of ≤ 0.125 μmol/L for juglone (1a), 5,8-dimethoxy-1,4-naphthoquinone (1f), and 7-methyl-5-acetoxy-1,4-naphthoquinone (3c), a strong antibacterial activity against S. aureus was observed. All 1,4-naphthoquinone derivatives exhibited a strong antibacterial activity, with MIC values ranging between 15.625 and 500 μmol/L and EC₅₀ values ranging between 10.56 and 248.42 μmol/L. Most of the synthesized compounds exhibited strong antibacterial activities against S. aureus. Among these compounds, juglone (1a) showed the strongest antibacterial activity. The results from mechanistic investigations indicated that juglone, a natural naphthoquinone, caused cell death by inducing reactive oxygen species production in bacterial cells, leading to DNA damage. In addition, juglone could reduce the self-repair ability of bacterial DNA by inhibiting RecA expression. In addition to having a potent antibacterial activity, juglone exhibited low cytotoxicity in cell-based investigations. In conclusion, juglone is a strong antibacterial agent with low toxicity, indicating that its application as a bactericidal agent may be associated with low health risks and aquatic toxicity.     

Effect of Zn salts and hydrolyzing agents on the morphology and antibacterial activity of zinc oxide nanoparticles

Environmental Chemistry Letters - Zinc oxide nanoparticles (ZnONPs) are considered safe as antibacterials. Those nanoparticles should preferably have uniform size and shape, but conditions to...     

Bacterial toxicity testing and antibacterial activity of parabens

Parabens are used because of their antimicrobial effects, yet they have multiple adverse effects. The aim of this work was to evaluate the bactericidal activity and bacterial toxicity of the most common parabens: methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben and phenylparaben. The bactericidal action was evaluated by means of the dilution-neutralization method against Escherichia coli and Staphylococcus aureus, and the biotest of inhibition of growth of E. coli was applied for the bacterial toxicity assay. Bactericidal concentrations were reached only for propylparaben, butylparaben and isobutylparaben. The toxicity study showed methylparaben to be the least toxic, whereas the most toxic one was phenylparaben. It can be concluded that the disinfectant activity of the parabens studied is insignificant against S. aureus and E. coli. Acute toxicity is very low, and the inhibitory effect is weak. Our results provide information about the risk–benefit balance of parabens use.     

Large-scale synthesis and antibacterial activity of fungal-derived silver nanoparticles

There is a demand for environmentally friendly processes to synthesize nanoparticles. Here, we synthesized silver nanoparticles using encapsulated biomass beads of Phoma exigua var. exigua. Nanoparticles were characterized by nanoparticle tracking and analysis (NTA), Fourier-transform infrared spectroscopy, X-ray diffraction, transmission electron microscopy and zeta potential. Results of NTA show that nanoparticle size was homogenous. Concerning nanoparticle stability, zeta potential decreased with batch number. Silver nanoparticles exhibited an antibacterial activity against Escherichia coli and Staphylococcus aureus. Overall, the encapsulation of fungal biomass by calcium alginate for the batch synthesis of silver nanoparticles was easy, cost-effective, eco-friendly and suitable for the large-scale synthesis of silver nanoparticles. We have also demonstrated the reusability of the fungal biomass during biosynthesis of silver nanoparticles using the sodium alginate encapsulation method.     

Seasonal changes in antibacterial activity of North Sea water

During 1969 and 1970, the antibacterial activity of North Sea water was investigated at Helgoland (southern North Sea). Tests were performed with resting cells of Escherichia coli, Staphylococous aureus and Serratia marinorubra, inoculated in freshly sampled sea water used raw or after filter sterilization. Simultaneously, growth of indigenous bacterial populations which occurred in the presence, as well as in the absence (only 1970), of test bacteria was controlled. Seasonal changes in inactivation of test cells and multiplication of marine bacteria were correlated with the life cycles of several diatom species. Breakdown of phytoplankton flowerings produced the most pronounced influence on antibacterial activity of sea water. Sometimes, enhancement of kill rate could be established during growth periods of various algal species, too. From the results obtained, it is concluded that the inactivation capacity of sea water depends, to a considerable degree, on the availability of nutritive organic matter, the concentration of which changes according to phytoplankton development. Strain-specific differences in resistance to inimical action of sea water are, in part, correlated with the ability of test cells to use, and to compete with, marine bacteria for nutrients from the sea. A somewhat modified interpretation of antibacterial activity of sea water is presented.     

Darkened Xenopus tadpoles appeared with neurochemical agents

Skin darkened tadpoles sometimes appear spontaneously. Darkened was artificially induced in Xenopus larvae by yohimbine or chlorpromazine. These phenomena look like that are seen at pinealectomized or hypothalamus separated Xenopus larva. In this experiment, such a morphological color changed Xenopus larva is suggested by cause of inhibition of alpha2-adrenargic receptor or dopamine receptor from gastrula stages.     

Microwave-assisted synthesis of biodegradable and antibacterial thiophene,furan and thiazole derivatives

Environmental Chemistry Letters - The rise of bacterial resistance to common clinical antibiotics is calling for alternative techniques to synthesize antibacterial drugs with high biodegradability....     

Mineralogical variables that control the antibacterial effectiveness of a natural clay deposit

As antibiotic-resistant bacterial strains emerge and pose increased global health risks, new antibacterial agents are needed as alternatives to conventional antimicrobials. Naturally occurring antibacterial clays have been identified which are effective in killing antibiotic-resistant bacteria. This study examines a hydrothermally formed antibacterial clay deposit near Crater Lake, OR (USA). Our hypothesis is that antibacterial clays buffer pH and Eh conditions to dissolve unstable mineral phases containing transition metals (primarily Fe²⁺), while smectite interlayers serve as reservoirs for time release of bactericidal components. Model pathogens (Escherichia coli ATCC 25922 and Staphylococcus epidermidis ATCC 14990) were incubated with clays from different alteration zones of the hydrothermal deposit. In vitro antibacterial susceptibility testing showed that reduced mineral zones were bactericidal, while more oxidized zones had variable antibacterial effect. TEM images showed no indication of cell lysis. Cytoplasmic condensation and cell wall accumulations of <100 nm particles were seen within both bacterial populations. Electron energy loss analysis indicates precipitation of intracellular Fe³⁺-oxide nanoparticles (<10 nm) in E. coli after 24 h. Clay minerals and pyrite buffer aqueous solutions to pH 2.5–3.1, Eh > 630 mV and contain elevated level (mM) of soluble Fe (Fe²⁺ and Fe³⁺) and Al³⁺. Our interpretation is that rapid uptake of Fe²⁺ impairs bacterial metabolism by flooding the cell with excess Fe²⁺ and overwhelming iron storage proteins. As the intracellular Fe²⁺ oxidizes, it produces reactive oxygen species that damage biomolecules and precipitates Fe-oxides. The ability of antibacterial clays to buffer pH and Eh in chronic non-healing wounds to conditions of healthy skin appears key to their healing potential and viability as an alternative to conventional antibiotics.     

Effective antibacterial and antioxidant properties of methanolic extract of Laurus nobilis seed oil

This study was carried out to determine the in vitro antimicrobial and antioxidant activities of the essential oil, seed oil, and methanolic extract of seed oil obtained from Laurus nobilis L. (Lauraceae). The methanolic extract of seed oil exhibited more effective antibacterial activity comparing to essential oil and seed oil, GC-MS analyses of the essential oil resulted in the identification of 25 compounds. 1.8-Cineol (44.72%), a-Terpinyl acetate (12.95%), Sabinene (12.82%) were the main components. The fatty acid composition was characterized with the high content of linoleic acid (40.79%) and lauric acid (38.08%). The 50% (IC50) inhibition activity of the essential oil on the free radical DPPH was determined as 94.655 mg ml(-1), whereas IC50 value of methanolic extract of seed oil was found unstable. In the case of the linoleic acid system, oxidation of linoleic acid was inhibited by essential oil and methanolic extract of seed oil, which showed 64.28 and 88.76% inhibition, respectively. The inhibition value of the methanolic extract of seed oil was quite close to the synthetic antioxidant BHT, 92.46% inhibition.     

Unraveling the antibacterial mode of action of a clay from the Colombian Amazon

Natural antibacterial clays can inhibit growth of human pathogens; therefore, understanding the antibacterial mode of action may lead to new applications for health. The antibacterial modes of action have shown differences based on mineralogical constraints. Here we investigate a natural clay from the Colombian Amazon (AMZ) known to the Uitoto natives as a healing clay. The physical and chemical properties of the AMZ clay were compared to standard reference materials: smectite (SWy-1) and kaolinite (API #5) that represent the major minerals in AMZ. We tested model Gram-negative (Escherichia coli ATCC #25922) and Gram-positive (Bacillus subtilis ATCC #6633) bacteria to assess the clay’s antibacterial effectiveness against different bacterial types. The chemical and physical changes in the microbes were examined using bioimaging and mass spectrometry of clay digests and aqueous leachates. Results indicate that a single dose of AMZ clay (250 mg/mL) induced a 4–6 order of magnitude reduction in cell viability, unlike the reference clays that did not impact bacterial survival. AMZ clay possesses a relatively high specific surface area (51.23 m²/g) and much higher total surface area (278.82 m²/g) than the reference clays. In aqueous suspensions (50 mg clay/mL water), soluble metals are released and the minerals buffer fluid pH between 4.1 and 4.5. We propose that the clay facilitates chemical interactions detrimental to bacteria by absorbing nutrients (e.g., Mg, P) and potentially supplying metals (e.g., Al) toxic to bacteria. This study demonstrates that native traditional knowledge can direct scientific studies.