从荧光假单孢菌中分离Azomycin

近年来人们已认识到细菌能产生广泛的结构多样的抗生素。许多由真细菌产生的已知抗生素,例如放线菌目的产物已见报道。本文报道从荧光假单孢菌的培养液中分离Azomycin。而 Azomycin 最初是从肠系膜诺卡氏样菌和杀霉菌素链霉菌中分离到的。代号为 PB-6282的 Azomycin 产生菌是以 Matsusaka 市的河水中分离到的,经菌种分类鉴定为荧光假单孢菌,有如下特征:该菌需氧,革兰氏呈阴性,形成末端呈圆形的无孢子杆(0.5μm×1.0～2.0μm),并具有极     

细菌素产生菌的筛选及其细菌素的分离纯化

从香肠中分离得到一株产细菌素的乳酸片球菌，其发酵液经硫酸铵沉淀，CM—Sephadex C50阳离子交换柱层析后，得到的细菌素样品通过SDS—PAGE证明是一条带，分子量约20．83ku，该细菌素对热及酸碱稳定，易被酶降解而失去活性，对许多革兰氏阳性茵有较强的抑制作用，而对革兰氏阴性茵、酵母和霉没有作用。     

一种通用的试验菌培养基

在新抗生素筛选中,首先要找到具有抗菌活性的产生菌,因此经常采用革兰氏阳性细菌(G~+)、革兰氏阴性细菌(G~-)、分枝杆菌     

临床感染标本的常见病原菌分布及耐药性分析

目的 研究医院细菌谱及细菌耐药性的变迁,为抗菌药物的合理使用提供依据。方法 对2002年6月-2003年5月临床分离的1624株细菌及其耐药性进行回顾性分析。结果 革兰阴性杆菌占70.1％,革兰阳性球菌占29.9％,以铜绿假单胞菌、大肠埃希菌、克雷伯菌属、金黄色葡萄球菌等为主,耐药性菌株占29.1％;耐笨唑西林金黄色葡萄球菌(MRSA)占7 5％,药敏试验未发现耐万古霉素菌株出现;革兰氏阴性杆菌对头孢菌素一、二、三代抗生素耐药率均超过30％,亚胺培南对革兰氏阴性杆菌仍具有很强的抗菌活性。结论 近年来临床感染常见病原菌耐药形势已十分严峻,必须强调合理使用抗生素,重视细菌培养和药敏试验,增强临床用药的针对性。     

小单孢菌的选择性分离法

小单孢菌科被认为是新抗生素最重要的来源之一。许多氨基糖苷类抗生素如艮他霉素、紫苏霉素、相模湾霉素、抗生素G-418、G-52和威大霉素,大环内酯类抗生素如巨霉素、蔷薇霉素、幼霉素、抗生素Kx-41-B_2和M-4365及其它种类抗生素如碘霉素、四烯醇素和波卓霉素都已在小单孢菌属的菌株中发现。本文报道一种高效率的分离小单孢菌的方法。作者予先试验了大约35种抗生素对各种革兰氏阳性和阴性细菌包括小单孢菌在内     

多黏菌素异质性耐药的研究进展及临床意义

由于抗菌药物的大量使用,细菌的耐药性不断产生。如今,多黏菌素已成为抗多重耐药菌,尤其是碳青霉烯类耐药革兰阴性菌感染的最后一道防线药物。然而近几年来关于多黏菌素耐药的报道不断增加,并且已有研究发现多黏菌素的异质性耐药现象。异质性耐药是细菌由敏感到耐药的中间过程,常规的临床检验无法有效检测出异质性耐药,这对临床治疗用药造成了巨大的威胁,造成患者的反复感染和用药失败。但对其机制的研究较少,目前发现的主要与染色体上脂多糖(LPS)相关基因的突变,耐药基因的不稳定扩增和外排泵系统有关。本文总结了细菌异质性耐药,尤其是多黏菌素异质性耐药的研究及其临床意义。     

哌拉西林／舒巴坦对临床分离功的体外抗菌活性研究

目的比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林/舒巴坦(21),对临床分离309株需氧菌和30株厌氧菌的体外抗菌活性及其影响因素(研究哌拉西林/舒巴坦(21)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线).方法采用琼脂平板稀释法及肉汤稀释法测定MIC值,Nitrocefin纸片法测定细菌产生的β-内酰胺酶,时间杀菌曲线采用肉汤10倍稀释法.结果对临床分离的339株需氧菌及厌氧菌体外抗菌活性研究结果显示,哌拉西林及其与舒巴坦联合时,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC5o为1～4μg/ml,MIC90多数低于128μg/ml,优于革兰氏阴性杆菌,其MIC50为1～128μg/ml,MIC90多数高于128μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差,多数菌的MICso及MIC90分别为64及256μg/ml.对革兰氏阴性杆菌及厌氧菌,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林;对于革兰氏阳性球菌,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌.哌拉西林对产酶株的MIC高于非产酶株,联合舒巴坦后,产酶株MIC降低而非产酶株MIC变化不明显.不同比例联合的体外抗菌活性比较发现,以哌拉西林/舒巴坦21联合时效果较好.哌拉西林与舒巴坦21联合时,对多数临床分离菌的体外抗菌活性与阿莫西林/舒巴坦(21)的体外抗菌活性相当.本研究中,I临床分离细菌对哌拉西林的耐药率以假单胞菌属最高,达61.5%,其次是肠杆菌属细菌及大肠埃希氏菌,分别为50.8%、50.0%.哌拉西林联合舒巴坦后,所有细菌的耐药率明显下降.体外杀菌效果研究表明,当哌拉西林联合舒巴坦21时,4×MIC浓度作用于金葡球菌、大肠埃希氏菌及铜绿假单胞菌后,细菌数均随时间延长而呈指数级减少,在作用于8h细菌均被杀灭.1×MIC及2×MIC作用于以上细菌后,杀菌效果不及4×MIC.各种细菌的体外抗菌活性主要受培养基pH值及接种菌量的影响,几乎不受小牛血清白蛋白浓度的影响.结论哌拉西林/舒巴坦对β-内酰胺酶产生菌株的体外抗菌活性优于哌拉西林,以21联合效果最好,杀菌效果以4×MIC浓度最好,体外抗菌活性受培养基pH值及接种量的影响.     

微生物生物活性物质的研究进展

微生物生物活性物质包括抗生素和非抗生素生物活性物质。每年发现近百个新微生物活性物质 ,其中新的非抗生素生物活性物质逐年增多 ,并在数量上超过抗生素。虽然放线菌仍是主要产生菌 ,但近年来真菌产生的生物活性物质报道逐年增多。据已报道的资料 ,作者认为 :小单孢菌、稀有放线菌和多粘菌是寻找新微生物生物活性物质的重要菌源。海洋微生物产生的生物活性物质化学结构和生物活性的多样性以及化学物质的独特性吸引人们涉足海洋微生物索取新药物。尽管从海洋微生物筛选获得新药的机率高 ,但是关键要解决海洋微生物的分离方法和培养方法。除研发全新化学结构的新生物活性物质外 ,应对以往研究过、但被暂时舍弃或未深入研究的“老抗生素”重新评价并开发为新的微生物活性物质。     

哌拉西林/舒巴坦对临床分离菌的体外抗菌活性研究

目的　比较研究哌拉西林、舒巴坦、哌拉西林与舒巴坦不同比例联合及阿莫西林 /舒巴坦 (2∶1) ,对临床分离 3 0 9株需氧菌和 3 0株厌氧菌的体外抗菌活性及其影响因素 (研究哌拉西林 /舒巴坦 (2∶1)对金葡球菌、大肠埃希氏菌和铜绿假单胞菌的的杀菌曲线 )。方法　采用琼脂平板稀释法及肉汤稀释法测定MIC值 ,Nitrocefin纸片法测定细菌产生的 β 内酰胺酶 ,时间杀菌曲线采用肉汤 10倍稀释法。结果　对临床分离的3 3 9株需氧菌及厌氧菌体外抗菌活性研究结果显示 ,哌拉西林及其与舒巴坦联合时 ,对革兰氏阳性球菌及厌氧菌的体外抗菌活性MIC50 为 1～ 4μg/ml,MIC90 多数低于 12 8μg/ml,优于革兰氏阴性杆菌 ,其MIC50 为 1～12 8μg/ml ,MIC90 多数高于 12 8μg/ml;单用舒巴坦对各种细菌的体外抗菌活性极差 ,多数菌的MIC50 及MIC90 分别为 64及 2 5 6μg/ml。对革兰氏阴性杆菌及厌氧菌 ,哌拉西林与舒巴坦联合时体外抗菌活性明显优于单用哌拉西林 ;对于革兰氏阳性球菌 ,哌拉西林联合舒巴坦后体外抗菌活性改善不如革兰氏阴性杆菌及厌氧菌。哌拉西林对产酶株的MIC高于非产酶株 ,联合舒巴坦后 ,产酶株MIC降低而非产酶株MIC变化不明显。不同比例联合的体外抗菌活性比较发现 ,以哌拉西林 /舒巴坦 2∶1联合时效果较好。     

我院常见细菌分离及耐药性分析

目的促进临床合理使用抗菌药物。方法根据细菌分离鉴定及药物敏感试验结果,按照革兰氏阳性（G＋）菌、革兰氏阴性（G-）菌分类,并对各类细菌按菌名、菌株数及耐药情况进行分析。结果共分离出微生物83株,其中细菌65株,真菌20株,G＋菌以葡萄球菌、肠球菌、链球菌为主,G-菌以大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌等为主,细菌耐药率较高。结论应加强临床抗菌药物的应用管理,控制耐药菌产生。     

Ribosomally synthesized antibacterial peptides in Gram positive bacteria

The emergence of multidrug-resistant pathogens that has caused a serious problem in hospitals worldwide, has intensified the search for novel drugs, in order to replace or to be used in complement with the existing antibiotics. In this connection much interest has been focused on a group of antimicrobial peptides, so-called bacteriocins. These antagonising peptides, which are gene-encoded in contrast to those made by multi-enzyme-complexes, share some common physico-chemical properties, such as being small, cationic, amphiphilic and often being membrane active. However, they differ greatly from each other in their primary sequence and exhibit an impressively large inhibitory spectrum which covers almost all bacterial genera, including many important pathogens and food-spoilage bacteria. Many of these peptides are produced by lactic acid bacteria, organisms which have been used by man from ancient time in diverse fermentation processes, to improve and/or prolong self-life of many food and feed products. Numerous bacteriocins have been purified and characterised in great detail, both at biochemical and genetic levels. Still, novel bacteriocins with new properties are reported in an increasing number in recent years. In this review we will give a brief status quo of the present knowledge on bacteriocin research; thus different aspects such as their diversity in nature, biochemical properties, modes of action, biosynthesis and genetics will be treated.     

Purification and genetic characterisation of the novel bacteriocin LS2 produced by the human oral strain Lactobacillus salivarius BGHO1

The aim of this study was to investigate the antimicrobial potential of Lactobacillus salivarius BGHO1, a human oral strain with probiotic characteristics and a broad inhibitory spectrum both against Gram-positive and Gram-negative pathogens. Here we present the bacteriocin LS2, an extremely pH- and heat-stable peptide with antilisterial activity. LS2 is a novel member of the class IId bacteriocins, unique among all currently characterised bacteriocins. It is somewhat similar to putative bacteriocins from several oral streptococci, including the cariogenic Streptococcus mutans. LS2 is a 41-amino-acid, highly hydrophobic cationic peptide of 4115.1Da that is sensitive to proteolytic enzymes. LS2 was purified from cells of strain BGHO1 by solvent extraction and reverse-phase chromatography. Mass spectrometry was used to determine the molecular mass of the purified peptide. N-terminal amino acid sequencing enabled identification of the LS2 structural gene bacls2 by a reverse genetics approach. Downstream of the bacls2 gene, two bacteriocin-like genes were found, named blp1a and blp1b, and one putative bacteriocin immunity gene named bimlp. We also present the identification of the 242-kb megaplasmid pMPHO1 by pulsed-field gel electrophoresis, which harbours the genes bacls2, blp1a, blp1b and bimlp. Two peptides with antimicrobial activity, whose approximate sizes corresponded to those of blp1a and blp1b, were identified only after culturing strain BGHO1 in a chemically defined medium. This study demonstrated the capacity of Lactobacillus salivarius BGHO1 to produce multiple bacteriocins and further established this strain as a promising probiotic candidate.     

海洋来源的放线菌次级代谢产物及其生物活性

放线菌是迄今最重要和最大的药用微生物种群。海洋放线茵生存于苛刻特殊的海洋环境，使其具备了复杂独特的代谢途径，其次级代谢产物在结构类型以及在生物活性等方面都呈现出与陆生放线茵不同的特点和多样性。多年来，诸多结构新颖、生物活性显著的天然活性产物持续从海洋来源放线茵代谢产物中被发现，这些活性化合物为新药研究提供了丰富的先导化合物，有些已进入研发阶段。近年，海洋放线茵活性产物的研究仍然是海洋微生物产物研究中值得关注的一个热点。本文按化舍物结构类型简要介绍了海洋来源放线茵代谢产物及其生物活性的研究概况。     

Natural peroxy anticancer agents

Present review describes research on novel natural anticancer agents isolated from terrestrial and marine sources. More than 120 cytotoxic anticancer compounds have shown confirmed activity in vitro tumor cell lines bioassay and are of current interest to Natural Cancer Institute for further in vivo evaluation. Intensive searches for new classes of pharmacologically potent agents produced by terrestrial and marine organisms have resulted in the discovery of dozens of compounds possessing high cytotoxic activities. However, only a limited number of them have been tested in pre-clinical and clinical trials. One of the reasons is a limited supply of the active ingredients from the natural sources. However, the pre-clinical and clinical development of many terrestrial and/or marine-derived natural products into pharmaceuticals is often hampered by a limited supply from the natural source. Total synthesis is of vital importance in these situations, allowing for the production of useful quantities of the target compound for further biological evaluation. With computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of terrestrial and marine peroxides as an important source of leads for drug discovery.     

Are bacteriocins underexploited? Novel applications for old antimicrobials

Bacteriocins are ribosomally synthesized (poly)peptides produced by almost all prokaryotic lineages. Bacteriocins from lactic acid bacteria (LAB) and bacteriocin-producer probiotic organisms have been thoroughly studied due to their wide spectra of action, the long-term use in food fermentations and the consideration of these microorganisms as beneficial for human beings. Most of the studies on the biotechnological application of diverse bacteriocins have been focused on their use as food preservatives, nisin being the prototype successfully used in alimentation. However, bacteriocins from LAB have demonstrated a remarkable potential as therapeutics for medical or veterinary uses, alone or in combination with classical antimicrobials. Their interest is even higher now that the resistance to the antibacterials used in therapeutics is growing. In this review we explore exciting opportunities for bacteriocin and probiotic applications, highlighting the possibilities for new and innovative research in order to give the necessary attention to this type of natural molecules that exhibit a great potential.     

海洋来源的荧光天然产物

近年来海洋天然产物越来越引起科学家们的关注。由于在珊瑚礁珊瑚和海葵等海洋无脊椎动物中具有荧光现象普遍,许多海洋天然产物除了药用和生物学价值外,还具有突出的荧光特性。本文从来源、发色团结构以及应用等方面进行综述,介绍了Ageladine A、Marmycin A、两种新型羟基蒽醌和Zoanthoxanthins等几种海洋来源的荧光小分子,以及代表性的海洋荧光蛋白GFP家族和藻胆蛋白。它们具有独特的光学性质将在生物医学领域广泛应用。     

海洋拟诺卡菌来源的天然产物

海洋拟诺卡菌由于其独特的代谢功能，成为海洋放线菌次级代谢产物的重要来源。根据2010-2013年初的海洋放线菌天然产物的统计表明，对拟诺卡菌的研究仅次于链霉菌。本文综述了从2001年的第一个海洋来源的拟诺卡菌天然产物至2018年6月17年间报道的65个海洋拟诺卡菌天然产物的微生物来源、结构及其生物活性。其结构包括吡喃酮类、二酮哌嗪类、多肽类等，其中吡喃酮类化合物是主要类型，占海洋拟诺卡菌天然产物总数的46%；而29%的海洋拟诺卡菌天然产物表现出抑菌、细胞毒、抗炎等生物活性。     

Novel antimicrobial peptide discovery using machine learning and biophysical selection of minimal bacteriocin domains

Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives. However, bacteriocins display diverse mechanisms of action, a narrow spectrum of activity, and inherent challenges in natural product isolation making in vitro verification of putative bacteriocins difficult. A subset of bacteriocins exert their antimicrobial effects through favorable biophysical interactions with the bacterial membrane mediated by the charge, hydrophobicity, and conformation of the peptide. We have developed a pipeline for bacteriocin-derived compound design and testing that combines sequence-free prediction of bacteriocins using machine learning and a simple biophysical trait filter to generate 20 amino acid peptides that can be synthesized and evaluated for activity. We generated 28,895 total 20-mer candidate peptides and scored them for charge, α-helicity, and hydrophobic moment. Of those, we selected 16 sequences for synthesis and evaluated their antimicrobial, cytotoxicity, and hemolytic activities. Peptides with the overall highest scores for our biophysical parameters exhibited significant antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. Our combined method incorporates machine learning and biophysical-based minimal region determination to create an original approach to swiftly discover bacteriocin candidates amenable to rapid synthesis and evaluation for therapeutic use.     

Marine-derived drugs in neurology

The oceans provide a rich source of structurally unique compounds that have demonstrated significant biological activities in a range of indications. In particular, the development of marine compounds is emerging as an important field for neurology. Several marine-derived compounds are currently in clinical trials or have been launched for the treatment of neuropathic pain, schizophrenia and Alzheimer's disease. This review describes the development of several of these compounds, specifically covering the conopeptides, anabaseine and omega-3 fatty acids for the potential treatment of various neurological disorders.     

Diving for drugs: tunicate anticancer compounds

The marine biosphere boasts tremendous biodiversity replete with structurally unique, active and selective secondary metabolites. Bioprospecting for antitumor compounds has been rewarding, and tunicates have been especially successful in yielding prospective cancer therapies. These compounds are now subjected to clinical trials in Europe and the USA. With the ongoing search for potent and specific anticancer drugs, in this article we discuss the unique perspectives, compounds and opportunities afforded by this rich source of potential pharmaceuticals. We discuss marine-derived antitumor drugs, their structures, and their various types and levels of antitumor activities in bench and bedside efforts.