抗菌肽作用机制的研究进展

抗菌肽是一类来源于多种生物、能有效杀灭病原体的小分子多肽,具有活性谱广、作用强且迅速、不易产生耐药等众多优点.作为新一代抗感染候选药物,抗菌肽的作用机制还未完全清楚,但目前有两种观点已得到公认,即胞膜渗透作用破坏胞膜结构完整性和作用于胞内不同靶点干扰细菌生长及代谢平衡.本文主要就抗菌肽理化性质、二级结构、作用机制以及后两者间的关系做一总结,以便更好的理解抗菌肽的构效关系,为合理设计抗菌肽提供理论基础.     

抗菌肽抗菌机制及其应用研究进展

抗菌肽是一类小分子肽,具有广谱的抗菌活性。以往对抗菌肽抗菌机制的研究主要集中在细菌细胞膜的作用上,包含"桶板"模型、"毯式"模型,"环形孔"模型和"凝聚"模型。近年来相继发现某些抗菌肽可以作用于细菌细胞内部,与核酸物质结合,阻断DNA复制、RNA合成;影响蛋白质合成;抑制隔膜、细胞壁合成,阻碍细胞分裂;抑制胞内酶的活性。本文从胞内机制和胞外机制两个角度对抗菌肽的抗菌机制进行综述,以期阐明各类抗菌肽的作用机制,为进一步研究菌株耐药性、杀菌效果及其杀菌机制提供科学根据。     

抗菌肽耐药性研究进展

抗菌肽是生物体产生的一类具有抵抗外源性病原体功能的小分子多肽,具有抗细菌、真菌、病毒、癌细胞等多种活性.近几年的研究发现细菌会对抗菌肽产生耐药性.本文就细菌的构成性耐药性机制和诱导性耐药性机制等研究进展进行综述.     

重组抗菌肽生物作用和机制的研究进展

抗菌肽是一类具有生物活性的小分子多肽,具有多种杀菌和抗肿瘤的活性,本文将从抗菌肽的结构、理化性质、生物活性、作用机制等方面简要概述抗菌肽的研究现状,为抗菌肽的后续开发提供一些参考。     

抗菌肽及抗菌肽转基因植物研究进展

抗菌肽是一类小分子多肽,在生物体内分布广泛,具有广谱的抗菌性,是生物体内天然防御系统的一部分。主要介绍了抗菌肽的性质,类型,作用机制及抗菌肽转基因植物的研究进展。     

抗菌肽在转基因动植物中的研究进展

抗菌肽是一类广泛存在于生物界的小分子短肽,具有广谱的抗菌、抗病毒、抗寄生虫及抗癌等生物活性.将抗菌肽基因转入动、植物体内,不仅可以提高动、植物的抗病能力,而且有望通过转基因动、植物来大量生产抗菌肽,具有重要的研究价值和广阔的应用前景.就抗菌肤的特性、抗菌机理及其在转基因动、植物中的研究做一简要的综述.     

细菌对抗菌肽的耐受机制

抗菌肽广谱、高特异、高生物活性等特点决定其具极大的临床应用潜力,然而抗菌肽的耐受是其药物开发必须重视和亟待克服的问题。从生物学的观点看,部分细菌可以产生抗菌肽,其必定存在逃避自身抗菌肽作用的机制;从进化的观点看,宿主和病原体之间是相互抑制、相互逃避、相互适应的关系,细菌在漫长的进化中会形成应对抗菌肽的特殊机制。抗菌肽对细菌存在多种作用机制,其核心是依赖于与细胞膜相互作用或进入细胞,进而改变膜完整性或干扰胞内生理生化反应导致细菌死亡;而细菌通过减弱抗菌肽结合、降低抗菌肽有效浓度等方式产生对抗菌肽的耐受。这些耐受机制也为抗菌肽类药物开发提供重要的启示。     

抗菌肽及其重组表达系统研究进展

抗菌肽作为一类具有多种生物学功能的小肽,具有分子量小、不含外源成分、不易产生耐药性等特性,成为近年来的研究热点。该文综述了抗菌肽的种类、作用机制及其重组表达系统等方面的研究进展,并对存在的热点问题进行了探讨。     

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。     

抗菌肽研究进展

抗菌肽研究进展傅南雁许家喜＊（北京大学化学与分子工程学院,北京１００８７１）关键词抗菌肽两亲螺旋青霉素的发现使人们对由病原微生物感染而引发的各类疾病不再束手无策,并由此发展了大量的β－内酰胺类抗生素,对保护人类健康作出了巨大贡献。但随着上述“传统抗生...     

抗菌肽的抗生物膜机理研究进展

生物膜,也称为生物被膜,是指附着于有生命或无生命物体表面被细菌胞外大分子包裹的有组织的细菌群体。与浮游菌相比,生物膜内的细菌对抗生素的耐受性提高了10–1000倍,是造成目前细菌耐药的主要原因之一。作为一种新型抗菌制剂,抗菌肽的使用为生物膜感染的治疗提供了一种新的思路和手段。抗菌肽在抑制生物膜形成、杀灭生物膜内细菌以及消除成熟生物膜的过程中发挥了独特的优势。文中分析了近30年的数据,从细菌生物膜的结构入手,对抗菌肽可能的抗生物膜机理进行了综述,以期为抗菌肽临床治疗生物膜感染提供一定参考。     

Branched antimicrobial peptides

Branched peptides E(RLAR)₂, E[E(RLAR)₂]₂, and E(KLAR)₂, E[E(KLAR)₂]₂ were synthesized on the basis of tetrapeptides RLAR and KLAR and glutamic acid bis(pentafluorophenyl) ester. Their minimal antimicrobial concentrations were shown to decrease along with increase in branching, achieving 12 μM for Escherichia coli cells, which is comparable to antimicrobial activities of temporin, magainin, and dermaseptin. The branched peptides were found not to act on human erythrocytes.     

抗菌肽活性及天然抗菌肽的改造

抗菌肽具有抗菌谱广、热稳定性强、分子量小及免疫原性小等特点,其杀菌机制独特,病原菌不易产生耐药性,有望开发成新一代肽类抗生素。本文主要综述了影响抗菌肽生物活性的生化性质,即螺旋度、疏水性、两亲性、正电荷数等,并从结构的角度论述了其对抗菌肽抑菌活性的影响。部分抗菌肽具有空间结构不稳定、溶血活性等缺点,限制了其临床应用。因此,对天然抗菌肽的改造也成为目前抗菌肽的研究热点,本文还综述了天然抗菌肽的改造方法。     

蜘蛛抗菌肽研究进展

蜘蛛活性多肽研究主要集中于蜘蛛毒液中作用于离子通道的神经毒素多肽。但近年来,一些蜘蛛抗菌肽不断被分离纯化,其结构和抗菌活性也被广泛深入研究,这将成为蜘蛛活性多肽研究领域的一个新热点。在蜘蛛毒液和血液中,存在不同种类的抗菌肽,其多肽长度、结构、抗菌作用各不相同。而且,有些抗菌肽甚至具有抗肿瘤作用。概述了蜘蛛抗菌肽在结构和功能方面的研究进展。     

Bacterial resistance to antimicrobial peptides

Antimicrobial peptides (AMPs) or host defense peptides (HDPs) are vital components of human innate defense system targeting human‐related bacteria. Many bacteria have various mechanisms interfering with AMP activity, causing resistance to AMPs. Since AMPs are considered as potential novel antimicrobial drugs, understanding the mechanisms of bacterial resistance to direct killing of AMPs is of great significance. In this review, a comparative overview of bacterial strategies for resistance to direct killing of various AMPs is presented. Such strategies include bacterial cell envelope modification, AMP degradation, sequestration, expelling, and capsule.     

Chlamydia-secreted protease CPAF degrades host antimicrobial peptides

Chlamydia trachomatis infection in the lower genital tract, if untreated, can ascend to the upper genital tract, potentially leading to complications such as tubal factor infertility. The ascension involves cell-to-cell spreading, which may require C. trachomatis organisms to overcome mucosal extracellular effectors such as antimicrobial peptides. We found that among the 8 antimicrobial peptides tested, the cathelicidin LL-37 that is produced by both urogenital epithelial cells and the recruited neutrophils possessed a most potent antichlamydial activity. Interestingly, this antichlamydial activity was completely inhibited by CPAF, a C. trachomatis-secreted serine protease. The inhibition was dependent on CPAF's proteolytic activity. CPAF selectively degraded LL-37 and other antimicrobial peptides with an antichlamydial activity. CPAF is known to secrete into and accumulate in the infected host cell cytoplasm at the late stage of chlamydial intracellular growth and may be released to confront the extracellular antimicrobial peptides before the intra-inclusion organisms are exposed to extracellular environments during host cell lysis and chlamydial spreading. Thus, the finding that CPAF selectively targets host antimicrobial peptides that possess antichlamydial activities for proteolysis suggests that CPAF may contribute to C. trachomatis pathogenicity by aiding in ascending infection.     

Molecular dynamics simulation of the membrane binding and disruption mechanisms by antimicrobial scorpion venom-derived peptides

Pandinin 2 (Pin2) is an alpha-helical polycationic peptide, identified and characterized from venom of the African scorpion Pandinus imperator with high antimicrobial activity against Gram-positive bacteria and less active against Gram-negative bacteria, however it has demonstrated strong hemolytic activity against sheep red blood cells. In the chemically synthesized Pin2GVG analog, the GVG motif grants it low hemolytic activity while keeping its antimicrobial activity. In this work, we performed 12 μs all-atom molecular dynamics simulation of the antimicrobial peptides (AMPs) Pin2 and Pin2GVG to explore their adsorption mechanism and the role of their constituent amino acid residues when interacting with pure POPC and pure POPG membrane bilayers. Starting from an α-helical conformation, both AMPs are attracted at different rates to the POPC and POPG bilayer surfaces due to the electrostatic interaction between the positively charged amino acid residues and the charged moieties of the membranes. Since POPG is an anionic membrane, the PAMs adhesion is stronger to the POPG membrane than to the POPC membrane and they are stabilized more rapidly. This study reveals that, before the insertion begins, Pin2 and Pin2GVG remained partially folded in the POPC surface during the first 300 and 600 ns, respectively, while they are mostly unfolded in the POPG surface during most of the simulation time. The unfolded structures provide for a large number of intermolecular hydrogen bonds and stronger electrostatic interactions with the POPG surface. The results show that the aromatic residues at the N-terminus of Pin2 initiate the insertion process in both POPC and POPG bilayers. As for Pin2GVG in POPC the C-terminus residues seem to initiate the insertion process while in POPG this process seems to be slowed down due to a strong electrostatic attraction. The membrane conformational effects upon PAMs binding are measured in terms of the area per lipid and the contact surface area. Several replicas of the systems lead to the same observations.     

抗菌肽的结构分析、抗菌机制及改造应用的研究进展

细菌感染已成为威胁人类健康的重要公共卫生问题之一,而抗生素的滥用又加快了细菌耐药性的进程。抗菌肽因其广谱抗菌活性、快速杀菌作用、低毒性和不易产生耐药性等特点受到了广泛关注。然而,抗菌肽的天然结构也预示了其应用存在一些限制,如易降解、不稳定、低渗透和高成本等。如何改良抗菌肽仍是需要解决的难题。本文从抗菌肽的来源和结构特征出发,分析了与抗菌相关的空间结构及其所对应的抗菌机制,总结了现有抗菌肽的改良策略,为寻求新型改良方案奠定基础。希望为今后抗菌肽的改造与临床应用提供新的思路和方向。