贻贝抗菌肽的研究进展

贻贝中存在多种抗菌肽,根据一级结构的不同分为4种：defensin(防卫肽)、mytilin、myticin和mytimycin。抗菌肽以前体的形式存在,在缺乏感染等刺激物的情况下。成熟前体以活性方式储存在血液中,当受到感染后便参与组织反应。它们的抗感染反应与哺乳动物吞噬细胞的作用相似,不同的抗菌肽具有不同的抗菌谱。抗菌肽是机体在进化过程中非特异性免疫系统中的一种。     

利用精氨酸和缬氨酸设计新型α-螺旋抗菌肽

摘要：【目的】抗菌肽是生命体的自身免疫系统的重要组成部分。其中两性的α-螺旋抗菌肽在抗菌肽家族中又占有重要的地位,发挥着重要的作用。为了得到具有更高抗菌活性同时具有很低细胞毒性的抗菌肽,根据α-螺旋二级结构衍生出来的螺旋轮模型,设计了一条在疏水一侧含有8个缬氨酸和亲水一侧含有5个精氨酸的新型16残基抗菌肽。【方法】测定了设计得到的新型抗菌肽的最小抑菌浓度、对于红细胞和哺乳动物肾细胞的细胞毒性以及杀菌动力学。 【结果】抗菌活性检测表明,新型抗菌肽VGR16显示了强并快速的杀菌作用,其最小抑菌浓度在16－64     

抗菌肽改良设计及抗炎作用的研究进展

抗菌肽因其具有广谱抗菌活性、不容易引起抵抗性,被认为是先天免疫系统对抗微生物感染的多功能工具。然而,天然抗菌肽存在抗菌活性低、稳定性低、溶血性高等问题,使其较难应用于临床,所以研究人员对抗菌肽进行改良设计以期获得更高抗菌活性、更低溶血活性的新型抗菌肽。另外,天然抗菌肽作为一类免疫效应因子而被发现,其表现出的抑菌、免疫调节、内毒素中和等作用,使得研究人员对抗菌肽在抗炎作用的研究表现出极大的兴趣。就抗菌肽的药物设计方法及抗炎作用机制进行综述。     

抗菌肽及其功能研究

抗菌肽是近年来发现的广泛存在于自然界的一类阳离子抗菌活性肽,越来越多的证据表明它们在宿主先天性免疫和适应性免疫中有着重要的作用。对抗菌肽的研究正不断深入。本文先从抗菌肽研究的历史背景出发,简要介绍了抗菌肽的一般特性;然后从抗菌肽的直接抗菌活性和免疫调节功能这两个方面重点阐述其在宿主防御过程中的作用,最后对抗菌肽的临床应用及前景做了一个概述。     

昆虫抗菌肽的功能、作用机理与分子生物学研究最新进展

昆虫虽然没有完善的免疫防御体系,但却具有高效的无细胞免疫系统。抗菌肽是昆虫免疫后血淋巴中的一类抗菌多肽,它具有分子量小,热稳定,水溶性好,无免疫原性,抗菌谱广等特点。现在,它被认为是从细菌到高等哺乳动物普遍存在的一类防御性多肽,称之为“第二防御体系”。抗菌肽不仅抗菌谱广,而且可以抑杀某些真菌、病毒及原虫,并对多种癌细胞及动物实体瘤有明显的杀伤作用,而不破坏正常细胞。近年来,对昆虫抗菌物质的研究,特别是对昆虫抗菌肽的研究已成为一个迅速发展的新领域,越来越引起人们的关注和重视。抗菌肽可望成为新一代的抗菌、抗病毒、抗癌药物。但天然抗菌肽的来源少,成本高,无法满足临床试用和基础研究的需要。因此通过 Ｄ Ｎ Ａ 重组技术来获得大量抗菌肽,成为人们普遍关注的焦点。同时,对抗菌肽抗菌、抗肿瘤机理的深入研究也越来越具有重大的理论意义和实际应用价值,前景十分广阔     

抗菌肽Cecropin及其在转基因植物抗菌中的应用

Cecropin抗菌肽,又名天蚕素,是一类具有抗菌能力的小分子多肽,热稳定性好,抗菌谱广,在各个应用领域已经得到广泛的研究。本文就Cecropin抗菌肽结构与功能的关系、作用机制和其在转基因植物抗菌领域中的应用进行综述,转基因植物表达Cecropin抗菌肽具有应用优势和实用价值,Cecropin抗菌肽分子结构与作用机制探索的深入能进一步促进转基因植物抗菌研究的发展。     

本期重点推介

昆虫抗菌肽因其重要的可开发利用价值愈来愈受到人们的重视。家蚕Bombyx mori基因组全测序完成后,经注释发现了35条拟抗微生物肽基因序列,但是这些拟抗微生物肽基因是否具有抗菌活性,是否与其他昆虫中鉴定报道的同种抗菌肽具有相似的抗菌谱和抗菌活性,在同一基因组中的同种抗菌     

蛙皮素-蜂毒素杂合肽基因在大肠杆菌中的克隆与诱导表达

抗菌肽 (Ａｎｔｉｂａｃｔｅｒｉａｌｐｅｐｔｉｄｅｓ)原指昆虫体内经诱导产生的一类分子量在 4ｋＤ左右 ,具有抗菌活性的碱性多肽物质[2 ] 。这类抗菌剂最初是从昆虫、哺乳动物、两栖动物等的防御系统中分离得到的。抗菌肽对革兰氏阳性及阴性细菌、病毒、原虫和发生病变的真核细胞等有杀伤作用 ,具有很强的广谱抑菌作用 ,但对正常哺乳动物细胞无杀伤作用[3 ] 。蛙皮素还具有抗肿瘤活性而没有溶血活性[4 ] ,虽然蜂毒素具有溶血活性 ,但其溶血功能区位于Ｃ端的亲水区域[5] ,两者的极性区域正好相反。据研究表明抗菌肽都会形成两亲螺旋结构的…     

动物抗菌肽

动物抗菌肽是有抗菌作用的小分子蛋白质 ,是宿主先天性非特异性防御系统的重要组分。机体受到损伤或病原微生物入侵时 ,能迅速产生抗菌肽杀伤入侵者。Ｂｏｍａｎ称抗菌肽是机体理想的第一道防线 ,因为抗菌肽的合成速度非常快 ,与以恒定的肽键合成速度相比较 ,抗菌肽的产生比ＩｇＭ快 10 0多倍。而且 ,小肽的扩散比大蛋白质和免疫细胞更加迅速 ,作用更显灵活。自 2 0世纪 80年代早期 ,天蚕素和防御素分离纯化鉴定以来 ,天然抗菌肽的研究引起了人们的极大兴趣。迄今为止 ,大约 2 0 0 0多种抗菌肽被分离出来 ,在哺乳动物、两栖类、昆虫中均已发…     

猪源抗菌肽PMAP-36的序列设计及其结构优化的研究进展

抗生素的耐药性和动物源性食品中的药物残留问题严重威胁全球公共卫生系统。因此,开发出不易产生耐药性、抗菌活性高的新型抗菌药物迫在眉睫。抗菌肽因其分子量小、抗菌谱广、不易产生耐药性等优点受到科学家们的广泛关注,但天然抗菌肽具有抗菌活性低、溶血活性和细胞毒性等缺陷。随着抗菌肽序列和结构的不断优化,多种具有显著体内外抗菌活性且安全高效的新型抗菌药物被研发出来。猪源抗菌肽PMAP-36是从猪骨髓细胞中分离出来的一种具有典型两亲性α-螺旋结构的高阳离子抗菌肽。本文就国内外关于猪源抗菌肽PMAP-36的序列设计及其结构优化等方面的研究进展进行综述。     

Simulating the antimicrobial mechanism of human β-defensin-3 with coarse-grained molecular dynamics

Human β-defensin-3 (HβD-3) is an endogenous antimicrobial peptide with potent and broad killing activity against various microorganisms, and thus, it is an attractive candidate for the development of novel peptide antibiotics, but its antimicrobial mechanism remains elusive. To characterize the mechanism, we used multi-microsecond coarse-grained simulations with the MARTINI force field. These simulations show HβD-3 peptides can form oligomers on the surface of bacterial membrane and make anionic lipids (POPG) clustered. Furthermore, two kinds of regions (one is composed of pure POPG lipids, and the other is enriched in POPE lipids) are formed in the membrane; on the border of them, there are some obvious defects, which result in the membrane disruption. By contrast, the simulations also reveal that the contacts between the HβD-3 peptides and mammalian membrane are not stable. These results provide biophysical insights into HβD-3 selectivity and suggest a possible antimicrobial mechanism.     

Phagocytosis of bacterial pathogens

Phagocytosis is an evolutionarily ancient, receptor-driven process, by which phagocytic cells recognize invading microbes and destroy them after internalization. The phagocytosis receptor Eater is expressed exclusively on Drosophila phagocytes and is required for the survival of bacterial infections. In a recent study, we explored how Eater can defend fruit flies against different kinds of bacteria. We discovered that Eater bound to certain types of bacteria directly, while for others bacterial binding was dependent on prior disruption of the bacterial envelope. Similar to phagocytes, antimicrobial peptides and lysozymes are ancient components of animal immune systems. Our results suggest that cationic antimicrobial peptides, as well as lysozymes, can facilitate Eater binding to live Gram-negative bacteria. Both types of molecules promote surface-exposure of bacterial ligands that otherwise would remain buried and hidden under an outer membrane. We propose that unmasking ligands for phagocytic receptors may be a conserved mechanism operating in many animals, including humans. Thus, studying a Drosophila phagocytosis receptor may advance our understanding of innate immunity in general.     

Phagocytosis of bacterial pathogens

Phagocytosis is an evolutionarily ancient, receptor-driven process, by which phagocytic cells recognize invading microbes and destroy them after internalization. The phagocytosis receptor Eater is expressed exclusively on Drosophila phagocytes and is required for the survival of bacterial infections. In a recent study, we explored how Eater can defend fruit flies against different kinds of bacteria. We discovered that Eater bound to certain types of bacteria directly, while for others bacterial binding was dependent on prior disruption of the bacterial envelope. Similar to phagocytes, antimicrobial peptides and lysozymes are ancient components of animal immune systems. Our results suggest that cationic antimicrobial peptides, as well as lysozymes, can facilitate Eater binding to live Gram-negative bacteria. Both types of molecules promote surface-exposure of bacterial ligands that otherwise would remain buried and hidden under an outer membrane. We propose that unmasking ligands for phagocytic receptors may be a conserved mechanism operating in many animals, including humans. Thus, studying a Drosophila phagocytosis receptor may advance our understanding of innate immunity in general.     

Differences in basal and ethanol-induced levels of opioid peptides in Wistar rats from five different suppliers

Mammalian cationic antimicrobial peptides have received increased attention over the last decade, due to their prokaryotic selectivity and decreased risk of microbial resistance. In addition, antimicrobial peptides display differential biological effects on mammalian immune cell function, such as migration, adhesion, and modulation of respiratory burst, which make them even more attractive as therapeutic agents. Synthetic combinatorial libraries provide a time-efficient and cost-effective source for these diverse molecules. The novel synthetic antimicrobial peptide, KSLW (KKVVFWVKFK-NH(2)), has been shown to display a broad spectrum of antimicrobial activity against Gram (+) and Gram (-) bacteria, fungi and viruses. In this study, we evaluated the alternative biological activity of the decapeptide on neutrophil migration and function. KSLW was demonstrated to be chemotactic for neutrophils in micromolar amounts, and neutrophil treatment with KSLW, after 1 min, resulted in significant increases in F-actin polymerization. KSLW was shown to inhibit oxygen radical production in PMA- and LPS-stimulated neutrophils. Future studies, to determine if KSLW regulates neutrophil phagocytosis, adhesion, and apoptosis, or examining the effect of KSLW on other mammalian cell types, such as cell populations of healing-impaired wounds, would provide significant insight for the potential therapeutic strategies offered by antimicrobial peptides.     

Structural features and biological activities of the cathelicidin-derived antimicrobial peptides

Cathelicidins are a numerous group of mammalian proteins that carry diverse antimicrobial peptides at the C-terminus of a highly conserved preproregion. These peptides, which become active when released from the proregion, display a remarkable variety of sizes, sequences, and structures, and in fact comprise representatives of all the structural groups in which the known antimicrobial peptides have been classified. Most of the cathelicidin-derived peptides exert a broad spectrum and potent antimicrobial activity and also bind to lipopolysaccharide and neutralize its effects. In addition, some of them have recently been shown to exert other activities and might participate in host defense also by virtue of their ability to induce expression of molecules involved in a variety of biological processes. This review is aimed at providing a general overview of the cathelicidins and of the peptides derived therefrom, with emphasis on aspects such as structure, biological activities in vitro and in vivo, and structure/activity relationship studies.     

LL-37, the only human member of the cathelicidin family of antimicrobial peptides

Antimicrobial peptides and their precursor molecules form a central part of human and mammalian innate immunity. The underlying genes have been thoroughly investigated and compared for a considerable number of species, allowing for phylogenetic characterization. On the phenotypical side, an ever-increasing number of very varied and distinctive influences of antimicrobial peptides on the innate immune system are reported. The basic biophysical understanding of mammalian antimicrobial peptides, however, is still very limited. This is especially unsatisfactory since knowledge of structural properties will greatly help in the understanding of their immunomodulatory functions. The focus of this review article will be on LL-37, the only cathelicidin-derived antimicrobial peptide found in humans. LL-37 is a 37-residue, amphipathic, helical peptide found throughout the body and has been shown to exhibit a broad spectrum of antimicrobial activity. It is expressed in epithelial cells of the testis, skin, the gastrointestinal tract, and the respiratory tract, and in leukocytes such as monocytes, neutrophils, T cells, NK cells, and B cells. It has been found to have additional defensive roles such as regulating the inflammatory response and chemo-attracting cells of the adaptive immune system to wound or infection sites, binding and neutralizing LPS, and promoting re-epthelialization and wound closure. The article aims to report the known biophysical facts, with an emphasis on structural evidence, and to set them into relation with insights gained on phylogenetically related antimicrobial peptides in other species. The multitude of immuno-functional roles is only outlined. We believe that this review will aid the future work on the biophysical, biochemical and immunological investigations of this highly intriguing molecule.     

LL-37, the only human member of the cathelicidin family of antimicrobial peptides

Antimicrobial peptides and their precursor molecules form a central part of human and mammalian innate immunity. The underlying genes have been thoroughly investigated and compared for a considerable number of species, allowing for phylogenetic characterization. On the phenotypical side, an ever-increasing number of very varied and distinctive influences of antimicrobial peptides on the innate immune system are reported. The basic biophysical understanding of mammalian antimicrobial peptides, however, is still very limited. This is especially unsatisfactory since knowledge of structural properties will greatly help in the understanding of their immunomodulatory functions. The focus of this review article will be on LL-37, the only cathelicidin-derived antimicrobial peptide found in humans. LL-37 is a 37-residue, amphipathic, helical peptide found throughout the body and has been shown to exhibit a broad spectrum of antimicrobial activity. It is expressed in epithelial cells of the testis, skin, the gastrointestinal tract, and the respiratory tract, and in leukocytes such as monocytes, neutrophils, T cells, NK cells, and B cells. It has been found to have additional defensive roles such as regulating the inflammatory response and chemo-attracting cells of the adaptive immune system to wound or infection sites, binding and neutralizing LPS, and promoting re-epthelialization and wound closure. The article aims to report the known biophysical facts, with an emphasis on structural evidence, and to set them into relation with insights gained on phylogenetically related antimicrobial peptides in other species. The multitude of immuno-functional roles is only outlined. We believe that this review will aid the future work on the biophysical, biochemical and immunological investigations of this highly intriguing molecule.     

Antimicrobial activity of three tick defensins and four mammalian cathelicidin-derived synthetic peptides against Lyme disease spirochetes and bacteria isolated from the midgut

In this study, chemically synthesized tick defensins and cathelicidin-derived mammalian peptides were used to investigate the activity spectrum against Borrelia garinii and symbiotic Stenotrophomonas maltophila. Synthetic tick defensins showed antimicrobial activity against Staphylococcus aureus but not B. garinii and S. maltophila. Mammalian peptides which have cationic property similar to tick defensins, showed antimicrobial activity similar to tick defensins. The antimicrobial peptides in ticks and mammalian hosts have common characteristics against microbial invasion in the innate immune system.