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。     

抗菌肽研究进展

抗菌肽是广泛存在于自然界生物中的一种具有抗菌、抗病毒和抗肿瘤活性的多态,由于抗菌肽具有普通抗生素所不具有的一系列优点,抗菌肽的研究已经成了现代学术和应用研究的一个热点。作者综述了抗菌肽的抗菌机制和应用研究等方面的内容。     

抗菌肽的基因工程研究进展

近年来细菌耐药性问题日趋严峻,寻找新型抗生素已迫在眉睫。抗菌肽是生物体产生的一种阳离子短肽,具有天然的抗菌活性。由于抗菌肽具有与传统抗生素不同的作用机制,不产生耐药性,因而具有重要的临床应用价值。但实践表明,抗菌肽的开发并非易事。针对近年来抗菌肽开发的基因工程策略和实践,尤其是大肠杆菌表达系统和酵母表达系统,进行了简要综述。     

抗菌肽药物工程化技术研究进展

尽管抗生素在畜牧业疾病防治中的主导地位在短期内不会动摇,但病原菌耐药性形成与快速发展让抗菌肽成为近年新药研发热点之一。作为一种在生物体内广泛存在的天然免疫物质,抗菌肽具有抗菌、抗病毒、抗肿瘤和免疫调节等功能,由于药效短、对蛋白酶敏感、细胞毒性高等缺陷而限制其应用。本文综述了抗菌肽基因工程技术、聚乙二醇(PEG)化、靶向性改造和固定化等工程技术在抗菌肽新药开发中的应用研究进展,以促进抗菌肽产业化。     

家蚕抗菌肽的特性与应用

家蚕抗菌肽是在抗菌、抗病毒和抗肿瘤方面具有重要的潜在应用价值的活性肽。家蚕抗菌肽抗菌谱广,由于抗菌肽有普通抗生素所不具有的一系列优点。其研究已经成热点。该文综述了冢蚕抗菌肽理化性质、结构与功能、作用机埋以及应用前景。     

家蝇幼虫抗菌肽的抗菌谱及其与抗生素的协同作用研究

研究3种家蝇幼虫抗菌肽的抗菌谱以及每种抗菌肽的最小抑菌浓度(MIC),初步探讨3种抗菌肽分别与青霉素、链霉素相结合后对抗菌活性的影响,并采用分级抑制浓度指数(Fractionalinhibitoryconcentrationindex,FIC)来定量检测抗菌肽与抗生素之间的抗菌作用关系。结果表明3种抗菌肽的抗菌谱不同,不同的抗菌肽对不同病原菌的抗菌活性不同。3种抗菌肽与链霉素、青霉素之间的抗菌协同关系因细菌种类不同。抗菌肽与抗生素之间并不是都存在协同关系,有些不相关,甚至表现为对抗关系,表明抗菌肽、抗生素与细菌三者的相互作用关系非常复杂。     

抗菌肽及其临床应用前景

传统抗生素的广泛运用导致了耐药菌株的大量增加,迫切要求新型抗生素的出现。抗菌肽是广泛存在于生物体内的小分子多肽,是天然免疫系统的重要组成部分。它不仅具有广谱杀菌作用,甚至能够抑杀真菌、寄生虫、含包膜病毒以及肿瘤细胞。抗菌肽通过与致病菌胞膜的结合形成跨膜离子通道,导致了细胞内外的离子交换最终引起细胞死亡。由于它作用迅速,选择性强,而且很少有耐药性的发生,很有可能成为新一代的抗菌药物。本文简述了抗菌肽的结构特点,抗菌作用机制,生物学功能和临床应用方面的最新进展以及进一步就抗菌肽作为新型抗生素所面临的问题进行了探讨。     

东北林蛙皮肤中一类新抗菌肽cDNA的克隆及成熟肽的预测

为进一步研究和开发高效广谱天然抗生素的抗菌肽,本文克隆东北林蛙(Rana dybowskii)的抗菌肽基因,并预测其成熟肽的有关性质。根据蛙属抗菌肽信号肽末端序列设计简并引物,以RT-PCR技术扩增皮肤中抗菌肽的cDNA,并进行克隆测序。用生物信息学软件分析cDNA序列特点,预测成熟肽的理化性质。研究发现一种长度为28个氨基酸残基的新抗菌肽dybowsin-1,该肽具有Rana box结构;与已发现的抗菌肽仅有35%的同源性;理论等电点在9.70-10.01之间;均呈阳离子性;从第3或4个氨基酸开始到第16个氨基酸形成α-螺旋结构,极性氨基酸位于螺旋轮的一侧,非极性氨基酸位于螺旋轮的另一侧;具有N-端疏水、C-端亲水的两亲性。一个个体表达5条cDNA序列编码3种不同的dybowsin-1分子,显示出该抗菌肽表达的多样性。序列分析显示,该抗菌肽可能由多基因座位编码。     

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。     

抗菌肽的研究进展

抗菌肽是一大类具有新型抗菌机理的抗生素,本文综述了抗菌肽的分类情况,抗菌肽的作用机制,以及部分正在开发的抗菌肽品种。     

Antimicrobial peptides from amphibian skin: an expanding scenario

Many organisms employ antimicrobial peptides to fend off microbial pathogens. Amphibian skin is one of the most generous sources of these peptides. In the past couple of years, intriguing additional insights on various aspects of frog skin peptides have been reported. Several novel molecules, often with unprecedented structural features, have been discovered. Studies focusing on the factors that regulate the in vivo synthesis of skin peptides in response to infection have gained in prominence. Moreover, recent results indicate new possibilities for the development of effective human therapeutics based on antimicrobial peptides and partially disclosed the biotechnological potential of these molecules.     

Bioprospecting the American Alligator (Alligator mississippiensis) Host Defense Peptidome

Cationic antimicrobial peptides and their therapeutic potential have garnered growing interest because of the proliferation of bacterial resistance. However, the discovery of new antimicrobial peptides from animals has proven challenging due to the limitations associated with conventional biochemical purification and difficulties in predicting active peptides from genomic sequences, if known. As an example, no antimicrobial peptides have been identified from the American alligator, Alligator mississippiensis, although their serum is antimicrobial. We have developed a novel approach for the discovery of new antimicrobial peptides from these animals, one that capitalizes on their fundamental and conserved physico-chemical properties. This sample-agnostic process employs custom-made functionalized hydrogel microparticles to harvest cationic peptides from biological samples, followed by de novo sequencing of captured peptides, eliminating the need to isolate individual peptides. After evaluation of the peptide sequences using a combination of rational and web-based bioinformatic analyses, forty-five potential antimicrobial peptides were identified, and eight of these peptides were selected to be chemically synthesized and evaluated. The successful identification of multiple novel peptides, exhibiting antibacterial properties, from Alligator mississippiensis plasma demonstrates the potential of this innovative discovery process in identifying potential new host defense peptides.     

Advances in antimicrobial peptide immunobiology

Antimicrobial peptides are ancient components of the innate immune system and have been isolated from organisms spanning the phylogenetic spectrum. Over an evolutionary time span, these peptides have retained potency, in the face of highly mutable target microorganisms. This fact suggests important coevolutionary influences in the host-pathogen relationship. Despite their diverse origins, the majority of antimicrobial peptides have common biophysical parameters that are likely essential for activity, including small size, cationicity, and amphipathicity. Although more than 900 different antimicrobial peptides have been characterized, most can be grouped as belonging to one of three structural classes: (1) linear, often of alpha-helical propensity; (2) cysteine stabilized, most commonly conforming to beta-sheet structure; and (3) those with one or more predominant amino acid residues, but variable in structure. Interestingly, these biophysical and structural features are retained in ribosomally as well as nonribosomally synthesized peptides. Therefore, it appears that a relatively limited set of physicochemical features is required for antimicrobial peptide efficacy against a broad spectrum of microbial pathogens.During the past several years, a number of themes have emerged within the field of antimicrobial peptide immunobiology. One developing area expands upon known microbicidal mechanisms of antimicrobial peptides to include targets beyond the plasma membrane. Examples include antimicrobial peptide activity involving structures such as extracellular polysaccharide and cell wall components, as well as the identification of an increasing number of intracellular targets. Additional areas of interest include an expanding recognition of antimicrobial peptide multifunctionality, and the identification of large antimicrobial proteins, and antimicrobial peptide or protein fragments derived thereof. The following discussion highlights such recent developments in antimicrobial peptide immunobiology, with an emphasis on the biophysical aspects of host-defense polypeptide action and mechanisms of microbial resistance.     

Experimental evolution of resistance to an antimicrobial peptide

A novel class of antibiotics based on the antimicrobial properties of immune peptides of multicellular organisms is attracting increasing interest as a major weapon against resistant microbes. It has been claimed that cationic antimicrobial peptides exploit fundamental features of the bacterial cell so that resistance is much less likely to evolve than in the case of conventional antibiotics. Population models of the evolutionary genetics of resistance have cast doubt on this claim. We document the experimental evolution of resistance to a cationic antimicrobial peptide through continued selection in the laboratory. In this selection experiment, 22/24 lineages of Escherichia coli and Pseudomonas fluorescens independently evolved heritable mechanisms of resistance to pexiganan, an analogue of magainin, when propagated in medium supplemented with this antimicrobial peptide for 600-700 generations.     

Application of antimicrobial peptides in agriculture and food industry

Antimicrobial peptides have captured the attention of researchers in recent years because of their efficiency in fighting against pathogens. These peptides are found in nature and have been isolated from a wide range of organisms. Furthermore, analogs or synthetic derivatives have successfully been developed on the basis of natural peptide patterns. Long use of pesticides and antibiotics has led to development of resistance among pathogens and other pests as well as increase of environmental and health risks. Antimicrobial peptides are under consideration as new substitutes for conventional pesticides and antibiotics. Many plants and animals have been manipulated with antimicrobial peptide-encoding genes and several pesticides and drugs have been produced based on these peptides. Such strategies and products may still have a long way to go before being confirmed by regulatory bodies and others need to surmount technical problems before being accepted as applicable ones. In spite of these facts, several cases of successful use of antimicrobial peptides in agriculture and food industry indicate a promising future for extensive application of these peptides. In this review, we consider the developing field of antimicrobial peptide applications in various agricultural activities.     

Prediction of Antimicrobial Activity of Synthetic Peptides by a Decision Tree Model

Antimicrobial resistance is a persistent problem in the public health sphere. However, recent attempts to find effective substitutes to combat infections have been directed at identifying natural antimicrobial peptides in order to circumvent resistance to commercial antibiotics. This study describes the development of synthetic peptides with antimicrobial activity, created in silico by site-directed mutation modeling using wild-type peptides as scaffolds for these mutations. Fragments of antimicrobial peptides were used for modeling with molecular modeling computational tools. To analyze these peptides, a decision tree model, which indicated the action range of peptides on the types of microorganisms on which they can exercise biological activity, was created. The decision tree model was processed using physicochemistry properties from known antimicrobial peptides available at the Antimicrobial Peptide Database (APD). The two most promising peptides were synthesized, and antimicrobial assays showed inhibitory activity against Gram-positive and Gram-negative bacteria. Colossomin C and colossomin D were the most inhibitory peptides at 5 μg/ml against Staphylococcus aureus and Escherichia coli. The methods described in this work and the results obtained are useful for the identification and development of new compounds with antimicrobial activity through the use of computational tools.     

抗菌肽结构改造与人工智能研发策略

抗菌肽是一类广泛存在于生物体内的小分子肽,参与构成生物体先天免疫,可以有效抵抗病原微生物的入侵。抗菌肽具有广谱抗菌活性,且不易产生耐药性等特点,在治疗感染性疾病方面具有独特的优势,有望成为理想的抗感染药物。然而,由于部分抗菌肽尚存在稳定性差、毒性高等问题,限制了抗菌肽的广泛应用。由于人工智能算法能有效合成具有高稳定性、低毒性的抗菌肽,在探索天然抗菌肽中展现了巨大的潜力,因此本文简述了抗菌肽的抗菌机制、结构改造以及利用机器学习和深度学习等人工智能算法进行新型抗菌肽研发的优化策略,以期为抗菌肽结构优化及研发提供新思路。     

蛙皮抗菌肽促胰岛素分泌功能研究进展

随着对蛙皮抗菌肽功能研究的不断深入,陆续发现部分肽具有促胰岛素分泌活性,该活性对于2型糖尿病治疗具有较好的应用前景。蛙皮抗菌肽即可以通过克服注射胰岛素产生的低血糖反应,又能改善2型糖尿病胰岛素抵抗的问题,这使其有希望成为安全、高效治疗2型糖尿病药物的新药物。本文综述了具有促胰岛素分泌功能的蛙皮抗菌肽的序列特征和工作机制的研究进展,为进一步开展相关研究提供参考。