两栖类动物Cathelicidins家族 抗菌肽研究进展

两栖类动物皮肤裸露和湿润的特性易于微生物的生长,它们为了抵御病原微生物的侵袭,在长期自然进化过程中形成了以抗菌肽(AMPs)为主要防御机制的免疫系统。抗菌肽广泛分布于动物、植物、微生物中,是生物用于抵御细菌、真菌、病毒和原虫等病原体侵袭的重要武器之一,在进化上是一类非常古老而有效的天然防御物质。Cathelicidins是脊椎动物特有的重要抗菌肽家族之一,除具有高效广谱的抗菌活性,还具有如抗炎、抗氧化、伤口修复、抑制组织损伤和促进血管生成等多种重要活性,因此Cathelicidins家族抗菌肽已成为抗感染多肽类新药的研发热点。本文将从两栖类动物Cathelicidins家族抗菌肽的一般特点、来源分布、生物合成与结构、生物学活性、作用机制及应用前景等几个方面,综合阐述国内外的研究动态。     

类弹性隆蛋白ELPs融合表达在抗菌肽分离纯化中的应用(简报)

抗菌肽(Antimierobial polypeDtides,AMPs)是两性带电分子,广泛存在于多种生物体内,具有广谱抗菌、调节免疫、抑制肿瘤等多种生物学功能.一些抗菌肽不仅对耐药性的病原细菌有很好的抑制和杀灭作用,而且还对真菌、原生动物、病毒等有很好的抑制作用.     

类弹性蛋白ELPs融合表达在抗菌肽分离纯化中的应用（简报）

抗菌肽（Antimicrobial polypeptides,AMPs）是两性带电分子,广泛存在于多种生物体内,具有广谱抗菌、调节免疫、抑制肿瘤等多种生物学功能。一些抗菌肽不仅对耐药性的病原细菌有很好的抑制和杀灭作用,而且还对真菌、原生动物、病毒等有很好的抑制作用。近年研究还发现,某些抗菌肽还可选择性杀伤肿瘤细胞,     

抗菌肽的研究现状和挑战

抗菌肽(AMPs)广泛存在于生物体内,可以协助机体抵御外源微生物的侵害,是生物体先天性防御系统中的重要组成成分。普遍认为,抗菌肽通过膜损伤机制,破坏微生物细胞膜或细胞壁的完整性,达到抑杀微生物的目的。然而,越来越多的证据表明抗菌肽还存在非膜损伤机制,作用于胞内靶位点杀伤细胞。由于其独特的作用机制及广谱抗菌活性,抗菌肽被应用于各行各业。但是,抗菌肽的推广应用也面临着诸多难题,如生物稳定性、抗菌活性的维持和微生物耐受性等。主要对抗菌肽的种类、作用机制、微生物对抗菌肽耐受性的产生机制及抗菌肽的应用和挑战进行综述。     

阳离子抗菌肽的研究进展

阳离子抗菌肽(Cationic antibacterial peptides)是生物体抵御外源性病原微生物的入侵而产生的一类小分子阳离子多肽,与传统的抗生素相比具有分子量小、抗菌谱广、热稳定性好、抗菌机理独特等优点。本文结合当今阳离子抗菌肽的研究现状和发展前景,从阳离子抗菌肽的理化性质、作用机理及其设计合成等方面进行了综述。     

抗菌肽融合表达研究进展

抗菌肽抗菌谱广、活性稳定,且具有与抗生素不同的抗菌机制,在抑杀病原微生物的同时不易产生耐药性,因而在食品、饲料、医药等领域具有重要的应用价值。基因工程技术是降低抗菌肽生产成本的主要方式,其中融合表达在提高抗菌肽产量方面起到了重要作用。文中综述了抗菌肽融合表达的国内外研究进展,探讨了部分融合标签用于抗菌肽表达的策略,并对今后的发展提出了自己的看法。     

抗菌肽及其临床应用研究进展

抗菌肽是生物体在抵抗病原微生物的防御反应过程中产生的一类具有抗微生物活性的小分子多肽。抗菌肽是机体天然免疫系统的重要组成部分,具有广谱的抗革兰氏阳性、阴性菌活性,对真菌、某些有包膜的病毒、寄生虫以及肿瘤细胞也有抑制活性。抗菌肽具有不同于传统抗生素的独特抗菌机制,病原菌不宜对其产生耐药性,有可能成为一种新的抗生素替代品。介绍了抗菌肽的来源与分类、理化特性与生物学活性,并重点阐述其最新的临床应用进展。     

细菌抗菌肽耐药机制研究进展

细菌对传统抗生素的耐药程度十分严重,寻找克服耐药性的新型抗菌药物已成为当务之急。抗菌肽(antimicrobial peptides,AMPs)是当下较有前景的抗菌药物之一。虽然通常认为,AMPs优先攻击细胞膜的特点使其不会引起广泛的耐药性,但其对特定靶标的识别能力仍为基因突变和细菌耐药性的产生提供了可能。此外,一些细菌还显示出了抵御宿主AMPs的杀伤作用并与宿主细胞共存的能力,相应的细菌防御机制也使其对治疗性AMPs产生抗性,这种交叉抗性近年来也备受关注。这些耐药现象的发现均对AMPs的开发提出了新挑战。本综述就细菌对AMPs耐药的分子机制进行了研究进展的总结,并且对治疗性AMPs与宿主防御肽交叉抗性的相关机制研究进行了归纳,以期寻求新的对抗耐药性的策略。     

综述人工合成型抗菌肽及其药学应用研究进展

天然抗菌肽（antimicrobial peptides, AMPs）是一类小分子阳离子多肽,具备多种杀菌机制,呈现出高效、广谱的杀菌特性,在抑制耐药性细菌、制备新型抗菌素等方面具有重要的研究价值。以天然抗菌肽为蓝本,设计和开发的人工合成型抗菌肽可以有效克服天然抗菌肽对蛋白酶敏感、细胞毒性较大、生产成本高等缺陷,作为抗感染的潜在药物具有更广阔的应用前景。综述了目前主要的抗菌肽人工改造技术,包括化学修饰法、蛋白质工程技术、计算机分子模拟技术和从头设计最小化抗菌肽方法的研究进展,并对人工合成抗菌肽作为抗菌药物的应用现状进行了简介。     

两栖动物皮肤结构及皮肤抗菌肽

两栖动物皮肤在自然进化过程中形成了防御病原微生物的三套防御系统,相应地具有特定结构。皮肤抗菌肽是其中先天性防御系统的主要组成部分。本文概述了两栖动物皮肤结构特点以及皮肤抗菌肽在国内外的最新研究进展,重点介绍了两栖动物皮肤腺体和蛙皮抗菌肽的种类、分子结构、抗菌机理、基因表达调控及cDNA编码特点以及基因工程等。以期系统认识和了解这些方面的研究与进展。     

Plant antimicrobial peptides

Plant antimicrobial peptides (AMPs) are a component of barrier defense system of plants. They have been isolated from roots, seeds, flowers, stems, and leaves of a wide variety of species and have activities towards phytopathogens, as well as against bacteria pathogenic to humans. Thus, plant AMPs are considered as promising antibiotic compounds with important biotechnological applications. Plant AMPs are grouped into several families and share general features such as positive charge, the presence of disulfide bonds (which stabilize the structure), and the mechanism of action targeting outer membrane structures.     

The therapeutic applications of antimicrobial peptides (AMPs): a patent review

Antimicrobial peptides (AMPs) are small molecules with a broad spectrum of antibiotic activities against bacteria, yeasts, fungi, and viruses and cytotoxic activity on cancer cells, in addition to anti-inflammatory and immunomodulatory activities. Therefore, AMPs have garnered interest as novel therapeutic agents. Because of the rapid increase in drug-resistant pathogenic microorganisms, AMPs from synthetic and natural sources have been developed using alternative antimicrobial strategies. This article presents a broad analysis of patents referring to the therapeutic applications of AMPs since 2009. The review focuses on the universal trends in the effective design, mechanism, and biological evolution of AMPs.     

The expanding scope of antimicrobial peptide structures and their modes of action

Antimicrobial peptides (AMPs) are an integral part of the innate immune system that protect a host from invading pathogenic bacteria. To help overcome the problem of antimicrobial resistance, cationic AMPs are currently being considered as potential alternatives for antibiotics. Although extremely variable in length, amino acid composition and secondary structure, all peptides can adopt a distinct membrane-bound amphipathic conformation. Recent studies demonstrate that they achieve their antimicrobial activity by disrupting various key cellular processes. Some peptides can even use multiple mechanisms. Moreover, several intact proteins or protein fragments are now being shown to have inherent antimicrobial activity. A better understanding of the structure-activity relationships of AMPs is required to facilitate the rational design of novel antimicrobial agents.     

Cationic Antimicrobial Peptides in Penaeid Shrimp

Penaeid shrimp aquaculture has been consistently affected worldwide by devastating diseases that cause a severe loss in production. To fight a variety of harmful microbes in the surrounding environment, particularly at high densities (of which intensive farming represents an extreme example), shrimps have evolved and use a diverse array of antimicrobial peptides (AMPs) as part of an important first-line response of the host defense system. Cationic AMPs in penaeid shrimps composed of penaeidins, crustins, and anti-lipopolysaccharide factors are comprised of multiple classes or isoforms and possess antibacterial and antifungal activities against different strains of bacteria and fungi. Shrimp AMPs are primarily expressed in circulating hemocytes, which is the main site of the immune response, and hemocytes expressing AMPs probably migrate to infection sites to fight against pathogen invasion. Indeed, most AMPs are produced as early as the nauplii developmental stage to protect shrimp larvae from infections. In this review, we discuss the sequence diversity, expression, gene structure, and antimicrobial activities of cationic AMPs in penaeid shrimps. The information available on antimicrobial activities indicates that these shrimp AMPs have potential therapeutic applications in the control of disease problems in aquaculture.     

Cationic Antimicrobial Peptides in Penaeid Shrimp

Penaeid shrimp aquaculture has been consistently affected worldwide by devastating diseases that cause a severe loss in production. To fight a variety of harmful microbes in the surrounding environment, particularly at high densities (of which intensive farming represents an extreme example), shrimps have evolved and use a diverse array of antimicrobial peptides (AMPs) as part of an important first-line response of the host defense system. Cationic AMPs in penaeid shrimps composed of penaeidins, crustins, and anti-lipopolysaccharide factors are comprised of multiple classes or isoforms and possess antibacterial and antifungal activities against different strains of bacteria and fungi. Shrimp AMPs are primarily expressed in circulating hemocytes, which is the main site of the immune response, and hemocytes expressing AMPs probably migrate to infection sites to fight against pathogen invasion. Indeed, most AMPs are produced as early as the nauplii developmental stage to protect shrimp larvae from infections. In this review, we discuss the sequence diversity, expression, gene structure, and antimicrobial activities of cationic AMPs in penaeid shrimps. The information available on antimicrobial activities indicates that these shrimp AMPs have potential therapeutic applications in the control of disease problems in aquaculture.     

Effect of antimicrobial peptides on ATPase activity and proton pumping in plasma membrane vesicles obtained from mycobacteria

The potential usefulness of antimicrobial peptides (AMPs) as antimycobacterial compounds has not been extensively explored. Although a myriad of studies on AMPs from different sources have been done, some of its mechanisms of action are still unknown. Maganins are of particular interest since they do not lyse non-dividing mammalian cells. In this work, AMPs with well-recognized activity against bacteria were synthesized, characterized, purified and their antimycobacterial activity and influence on ATPase activity in mycobacterial plasma membrane vesicles were assessed. Using bioinformatics tools, a magainin-I analog peptide (MIAP) with improved antimicrobial activity was designed. The influence of MIAP on proton (H(+)) pumping mediated by F(1)F(0)-ATPase in plasma membrane vesicles obtained from Mycobacterium tuberculosis was evaluated. We observed that the antimycobacterial activity of AMPs was low and variable. However, the activity of the designed peptide MIAP against M. tuberculosis was 2-fold higher in comparison to magainin-I. The basal ATPase activity of mycobacterial plasma membrane vesicles decreased approximately 24-30% in the presence of AMPs. On the other hand, the MIAP peptide completely abolished the F(1)F(0)-ATPase activity involved in H(+) pumping across M. tuberculosis plasma membranes vesicles at levels similar to the specific inhibitor N,N' dicyclohexylcarbodiimide. These finding suggest that AMPs can inhibit the H(+) pumping F(1)F(0)-ATPase of mycobacterial plasma membrane that potentially interferes the internal pH and viability of mycobacteria.     

Antimicrobial peptides: clinical relevance and therapeutic implications

Antimicrobial peptides (AMPs) are molecules that provide protection against environmental pathogens, acting against a large number of microorganisms, including bacteria, fungi, yeast, virus and others. Two major groups of antimicrobial peptides are found in humans: cathelicidins and defensins. Recently, several studies have furnished information that besides their role in infection diseases, antimicrobial peptides play a role in diseases as diverse as inflammatory disorders, autoimmunity and cancer. Here, we discuss the role of antimicrobial peptides and vitamin D have in such complex diseases and propose their use should be more explored in the diagnosis and treatment of such conditions.     

Amphibian antimicrobial peptides and Protozoa: Lessons from parasites

Antimicrobial peptides (AMPs) from amphibians and other eukaryotes recognize pathogenicity patterns mostly related to differences in membrane composition between the host and a variety of bacterial, fungal and protozoan pathogens. Compared to the other two groups, protozoa are fairly neglected targets in antimicrobial chemotherapy, despite their role as causative agents for scourges such as malaria, amoebiasis, Chagas' disease or leishmaniasis. Herein we review the scarce but growing body of knowledge addressing the use of amphibian AMPs on parasitic protozoa, the adaptations of the protozoan to AMP pressure and their impact on AMP efficacy and specificity, and the current and foreseeable strategies for developing AMPs into practical therapeutic alternatives against parasitic disease.     

Extremely abundant antimicrobial peptides existed in the skins of nine kinds of Chinese odorous frogs

Peptide agents are regarded as hopeful candidates to solve life-threatening resistance of pathogenic microorganisms to classic antibiotics due to their unique action mechanisms. Peptidomic and genomic investigation of natural antimicrobial peptides (AMPs) from amphibian skin secretions can provide a large amount of structure-functional information to design peptide antibiotics with therapeutic potential. In the present study, we identified a large number of AMPs from the skins of nine kinds of Chinese odorous frogs. Eighty AMPs were purified from three different odorous frogs and confirmed by peptidomic analysis. Our results indicated that post-translational modification of AMPs rarely happened in odorous frogs. cDNAs encoding precursors of 728 AMPs, including all the precursors of the confirmed 80 native peptides, were cloned from the constructed AMP cDNA libraries of nine Chinese odorous frogs. On the basis of the sequence similarity of deduced mature peptides, these 728 AMPs were grouped into 97 different families in which 71 novel families were identified. Out of these 728 AMPs, 662 AMPs were novel and 28 AMPs were reported previously in other frog species. Our results revealed that identical AMPs were widely distributed in odorous frogs; 49 presently identified AMPs could find their identical molecules in different amphibian species. Purified peptides showed strong antimicrobial activities against 4 tested microbe strains. Twenty-three deduced peptides were synthesized and their bioactivities, including antimicrobial, antioxidant, hemolytic, immunomodulatory and insulin-releasing activities, were evaluated. Our findings demonstrate the extreme diversity of AMPs in amphibian skins and provide plenty of templates to develop novel peptide antibiotics.