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。     

抗菌肽的筛选策略及其应用研究进展

抗菌肽是生物体产生的、抵抗外源病原物侵袭并具有广谱抗微生物作用的多肽类物质,是天然免疫系统的重要组成部分。从首次发现抗菌肽以来,现在已经获得了上千个有不同活性的抗菌肽候选者。回顾和总结了抗菌肽筛选的策略,包括经典方法、差异显示法、基于核酸的方法以及基于生物信息学分析法等,并重点介绍了最近提出的一种高通量筛选方法。最后本文对抗菌肽的临床应用研究,尤其是对进入临床评价阶段的抗菌肽研究进展进行了综述。     

Human Antimicrobial Peptides: Defensins, Cathelicidins and Histatins

Antimicrobial peptides, which have been isolated from many bacteria, fungi, plants, invertebrates and vertebrates, are an important component of the natural defenses of most living organisms. The isolated peptides are very heterogeneous in length, sequence and structure, but most of them are small, cationic and amphipathic. These peptides exhibit broad-spectrum activity against Gram-positive and Gram-negative bacteria, yeasts, fungi and enveloped viruses. A wide variety of human proteins and peptides also have antimicrobial activity and play important roles in innate immunity. In this review we discuss three important groups of human antimicrobial peptides. The defensins are cationic non-glycosylated peptides containing six cysteine residues that form three intramolecular disulfide bridges, resulting in a triple-stranded β-sheet structure. In humans, two classes of defensins can be found: α-defensins and β-defensins. The defensin-related HE2 isoforms will also be discussed. The second group is the family of histatins, which are small, cationic, histidine-rich peptides present in human saliva. Histatins adopt a random coil conformation in aqueous solvents and form α-helices in non-aqueous solvents. The third group comprises only one antimicrobial peptide, the cathelicidin LL−37. This peptide is derived proteolytically from the C-terminal end of the human CAP18 protein. Just like the histatins, it adopts a largely random coil conformation in a hydrophilic environment, and forms an α-helical structure in a hydrophobic environment.     

Antimicrobial Peptides: Successes, Challenges and Unanswered Questions

Multidrug antibiotic resistance is an increasingly serious public health problem worldwide. Thus, there is a significant and urgent need for the development of new classes of antibiotics that do not induce resistance. To develop such antimicrobial compounds, we must look toward agents with novel mechanisms of action. Membrane-permeabilizing antimicrobial peptides (AMPs) are good candidates because they act without high specificity toward a protein target, which reduces the likelihood of induced resistance. Understanding the mechanism of membrane permeabilization is crucial for the development of AMPs into useful antimicrobial agents. Various models, some phenomenological and others more quantitative or semimolecular, have been proposed to explain the action of AMPs. While these models explain many aspects of AMP action, none of the models captures all of the experimental observations, and significant questions remain unanswered. Here, we discuss the state of the field and pose some questions that, if answered, could speed the discovery of clinically useful peptide antibiotics.     

抗菌肽的设计及其应用

抗菌肽(AMP)是生物体内先天免疫系统的一个组成部分,保护机体免受致病微生物的入侵.抗菌肽具有很强的广谱抗菌活性,可抑制革兰氏阳性菌、革兰氏阴性菌、真菌和病毒的生长.为克服微生物对抗生素耐药性的问题,目前阳离子抗菌肽已被考虑作为抗生素的潜在替代品.本文将阐述抗菌肽的作用机理、选择性抗菌肽的设计及其应用.     

Synthetic Antimicrobial Peptides: I. Antimicrobial Activity of Amphiphilic and Nonamphiphilic Cationic Peptides

Comparative antimicrobial properties of three artificial cationic synthetic antimicrobial peptides (SAMP): (RAhaR)₄AhaβA (where R is Arg, Aha is 6-aminohexanoic acid, βA is beta-alanine), (KFF)₃K and R₉F₂ with various amphiphilic properties have been studied relative to pathogenic strains of microorganisms: Gram-negative bacteria Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, and Salmonella enterica, Gram-positive bacteria Staphylococcus aureus, and pathogenic yeast fungus Candida albicans. The selectivity index (SI) values of the peptide preparations were calculated as the ratio of the 50% cytotoxic concentration (TC₅₀) towards eukaryotic host cells to the MIC₅₀ values of the testing antimicrobial peptides. The studied SAMPs appeared to be the most active against the pathogenic yeast fungus C. albicans and the bacterial strains St. aureus and P. aeruginosa. The SI values in these cases exceed 40. Some assumed molecular interactions of the studied SAMPs on the microbial cells have been considered, and possible pathways to increase their antimicrobial activity have been suggested. The proposed SAMPs can serve as a basis for the design and synthesis of new promising synthetic antimicrobial agents.     

昆虫抗菌肽结构、性质和基因调控

昆虫抗菌肽是昆虫先天免疫系统中非常重要的一类效应分子。昆虫抗菌肽带正电荷,分子量小,大多数少于100个氨基酸残基。根据结构可以将昆虫抗菌肽分为一些不同的家族。昆虫抗菌肽不同的抗菌谱表明,它具有不同的作用机制。以果蝇为模式生物研究表明,昆虫抗菌肽的基因调控涉及到多个信号通路及大量的信号分子。     

抗菌肽的抗菌机制及其临床应用

抗菌肽是广泛存在于生物体内的一种小分子肽, 具有广谱性、高效性、稳定性等特点, 其本身不易产生耐药性。不仅具有杀菌作用, 还能抑杀真菌、寄生虫、病毒以及肿瘤细胞且对正常细胞毒性较小。新颖抗生素发现的缺乏, 导致了大量耐药菌株的出现, 抗菌肽有可能成为一种新的抗生素替代品。本文介绍了抗菌肽的结构特点、生物活性, 并重点阐述了其抗菌机制及最新临床应用进展。     

新疆家蚕抗菌肽抗菌作用的超微结构观察及抗菌机理初探

为探讨基因工程表达的新疆家蚕(Bombyx mori)抗菌肽(cecropin-XJ)的抗菌机制,通过紫外分光光度法研究抗菌肽的抑菌动力学,并采用透射电镜观察抗菌肽作用于金黄色葡萄球菌(Staphylococcus aureus)后的超微结构,对抗菌肽抗菌机理进行初步探讨。结果表明,抗菌肽抑菌作用比较明显,抗菌肽的活性与作用时间有关。抗菌肽可能是通过"桶-板"模式渗透细胞膜,从而影响细胞膜的结构和功能,使细胞膜形成许多孔道,增强了金黄色葡萄球菌细胞的通透性,造成细胞内的原生质扩散,并从孔道向胞外渗漏,影响了细菌的代谢系统,从而起到抑菌、杀菌作用。抗菌肽使金黄色葡萄球菌细胞内容物大量渗漏而死亡,死亡细胞的细胞壁保持完整,表明细胞膜是抗菌肽作用的主要靶位点。     

LAMP: A Database Linking Antimicrobial Peptides

The frequent emergence of drug-resistant bacteria has created an urgent demand for new antimicrobial agents. Traditional methods of novel antibiotic development are almost obsolete. Antimicrobial peptides (AMPs) are now regarded as a potential solution to revive the traditional methods of antibiotic development, although, until now, many AMPs have failed in clinical trials. A comprehensive database of AMPs with information about their antimicrobial activity and cytotoxicity will help promote the process of finding novel AMPs with improved antimicrobial activity and reduced cytotoxicity and eventually accelerate the speed of translating the discovery of new AMPs into clinical or preclinical trials. LAMP, a database linking AMPs, serves as a tool to aid the discovery and design of AMPs as new antimicrobial agents. The current version of LAMP has 5,547 entries, comprising 3,904 natural AMPs and 1,643 synthetic peptides. The database can be queried using either simply keywords or combinatorial conditions searches. Equipped with the detailed antimicrobial activity and cytotoxicity data, the cross-linking and top similar AMPs functions implemented in LAMP will help enhance our current understanding of AMPs and this may speed up the development of new AMPs for medical applications. LAMP is freely available at: http://biotechlab.fudan.edu.cn/database/lamp.     

Antimicrobial Peptides,a Pool for Novel Cell Penetrating Peptides Development and Vice Versa

International Journal of Peptide Research and Therapeutics - Membrane active peptides are a family of peptides with ability to interact with plasma membrane. Cell penetrating peptides (CPPs)...     

Antimicrobial Peptides (AMPs): Roles,Functions and Mechanism of Action

International Journal of Peptide Research and Therapeutics - Antimicrobial peptides (AMPs) are a crucial part of innate immunity that exist in the most of living organisms. In fact, AMPs have...     

Anionic Antimicrobial and Anticancer Peptides from Plants

Anionic antimicrobial peptides (AAMPs) have been identified in a wide variety of plant species with net charges that range between ?1 and ?7 and structures that include: extended conformations, α-helical architecture and cysteine stabilized scaffolds. These peptides commonly exist as multiple isoforms within a given plant and have a range of biological activities including the ability to kill cancer cells as well as phytopathogenic bacteria, fungi, pests, molluscs, and other predatory species. In general, the killing mechanisms underpinning these activities are poorly understood although they appear to involve attack on intracellular targets such as DNA along with compromise of cell envelope integrity through lysis of the cell wall via chitin-binding and/or permeabilisation of the plasma membrane via lipid interaction. It is now becoming clear that AAMPs participate in the innate immune response of plants and make a major contribution to the arsenal of defence toxins produced by these organisms to compensate for their lack of some defence mechanisms possessed by mammals, such as mobility and a somatic adaptive immune system. Based on their biological properties, a number of potential uses for plant AAMPs have been suggested, including therapeutically useful anticancer agents and novel antimicrobial compounds, which could be utilized in a variety of scenarios, ranging from the protection of crops to the disinfection of hospital environments.     

Opioid Peptides: An Overview of Functional Significance

International Journal of Peptide Research and Therapeutics - Bioactive peptides have been reported to exhibit opioid-like activity and are termed as opioid peptides. Either these are produced...     

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。     

Focus: Microbiome: Metagenomic Assembly: Overview,Challenges and Applications

Advances in sequencing technologies have led to the increased use of high throughput sequencing in characterizing the microbial communities associated with our bodies and our environment. Critical to the analysis of the resulting data are sequence assembly algorithms able to reconstruct genes and organisms from complex mixtures. Metagenomic assembly involves new computational challenges due to the specific characteristics of the metagenomic data. In this survey, we focus on major algorithmic approaches for genome and metagenome assembly, and discuss the new challenges and opportunities afforded by this new field. We also review several applications of metagenome assembly in addressing interesting biological problems.     

昆虫抗菌肽研究和应用现状

昆虫在受到刺激或感染之后,在其血淋巴中会产生一种抗菌类物质,称抗菌肽。抗菌肽具有分子小、稳定性好、广谱抗菌、无毒副作用等特点,在农业、医药、食品等领域有广泛的应用前景。简要综述了昆虫抗菌肽的基础研究和应用现状。     

Yeast Phytases: Present Scenario and Future Perspectives

ABSTRACT

Phytases hydrolyze phytates to liberate soluble and thus readily utilizable inorganic phosphate. Although phytases are produced by various groups of microbes, yeasts being simple eukaryotes and mostly non-pathogenic with proven probiotic benefits can serve as ideal candidates for phytase research. The full potential of yeast phytases has not, however, been exploited. This review focuses attention on the present status of knowledge on the production, characterization, molecular characteristics, and cloning and over-expression of yeast phytases. Several potential applications of the yeast phytases in feeds and foods, and in the synthesis of lower myo-inositol phosphates are also discussed.     

Plant Volatiles: Recent Advances and Future Perspectives

Volatile compounds act as a language that plants use for their communication and interaction with the surrounding environment. To date, a total of 1700 volatile compounds have been isolated from more than 90 plant families. These volatiles, released from leaves, flowers, and fruits into the atmosphere and from roots into the soil, defend plants against herbivores and pathogens or provide a reproductive advantage by attracting pollinators and seed dispersers. Plant volatiles constitute about 1% of plant secondary metabolites and are mainly represented by terpenoids, phenylpropanoids/benzenoids, fatty acid derivatives, and amino acid derivatives. In this review we focus on the functions of plant volatiles, their biosynthesis and regulation, and the metabolic engineering of the volatile spectrum, which results in plant defense improvement and changes of scent and aroma properties of flowers and fruits.