鲎素抗菌肽多效协同抗菌机理的初步研究

为了研究鲎素的抗菌机制,采用紫外吸收法检测细菌与鲎素共同孵育前后大分子泄漏情况;采用透射电镜观察细菌和鲎素共同孵育前后细菌形态和结构的变化;采用紫外吸收法和凝胶电泳技术观察鲎素对细菌基因组DNA和质粒DNA结构的影响.结果表明,经鲎素处理的细菌,胞内生物大分子泄漏显著,细胞壁膜遭到不同程度的破坏;鲎素可与细菌基因组DNA和质粒DNA结合,高浓度鲎素可以使DNA发生断裂,进而使质粒DNA复制和转录功能受到抑制.由此可初步得出结论:鲎素抗菌肽抗菌机理是一种协同作用,包括使细菌细胞膜通透性发生变化、作用细胞质内生物功能物质、结合细胞遗传物质DNA、抑制复制转录等多效的协同的作用机制.     

抗菌肽的生物学特征与作用机制间的相关性

抗生素的耐药性已对人类健康和畜牧业发展构成威胁,而抗菌肽作为抗生素的替代品之一,以其不易使细菌产生耐药性、无残留及其独特的抑菌机制,获得广泛认可。本文对抗菌肽的带电荷量、二级结构、两亲性、疏水力矩等生物学特征与抑菌机制间的相关性,以及对抗菌肽直接杀伤作用和免疫调节作用机制作一综述。     

抗菌肽生物活性及其影响因素的研究进展

抗菌肽是基因编码、核糖体合成的小分子活性肽,不仅对细菌、真菌、病毒、支原体、衣原体、螺旋体及一些活性细胞具有杀伤活性,还具有抗感染、免疫调节、信号转导等生物学功能。然而,自身和外在的一些因素影响了抗菌肽的生物学活性,并在一定程度上制约了其临床应用。当前研究从抗菌肽自身结构及其与受体间的相互作用等方面入手,以期降低影响因素的不利水平,提高抗菌肽的生物学活性。本文就抗菌肽生物活性及其影响因素的研究进展作一综述。     

代谢解偶联剂在污水处理领域中的研究进展

代谢解偶联剂是一类能抑制细胞体内能量偶联磷酸化的化合物,其存在可打破细胞内分解代谢与合成代谢之间的能量偶联,呼吸链中电子传递所产生的能量不能完全用于二磷酸腺苷(ADP)的磷酸化,抑制细菌体内三磷酸腺苷(ATP)的合成。在污水处理领域中,代谢解偶联剂最早被用于污泥过程减量方向的研究,而近些年发现其可以控制膜生物反应器(MBR)内信号分子的浓度并抑制膜污染的形成。概述了代谢解偶联剂的研究历程,阐述了代谢解偶联剂抑制细菌体内ATP合成的作用机制,综述了代谢解偶联剂在污泥减量,膜污染控制及其对污染物去除和活性污泥性质影响等方面的研究进展,指出了代谢解偶联剂在污水处理领域未来的研究方向。     

抗菌肽生物活性及其影响因素

抗菌肽属于一种非特异性的免疫分子,具备广谱抗菌活性,其不仅对细菌、真菌、病毒、支原体以及部分肿瘤细胞有杀伤作用,还具有免疫调节、信号传导以及抗感染等多种功能。但是,抗菌肽自身与外在的部分因素,会导致抗菌肽的生物活性发生改变,制约了抗菌肽临床应用与发展。对此,从抗菌肽的生物活性着手,简要分析抗菌肽生物活性及其影响因素。     

昆虫抗菌肽的作用机制与应用研究进展

抗菌肽是进化上保守的天然免疫应答成分并且在所有生物体中存在。其抗菌谱宽,对病原性的病毒、细菌、寄生虫和真菌等病原微生物都具有拮抗活性。来源于昆虫的抗菌肽通常是带阳离子的,一般少于100个氨基酸。昆虫抗菌肽的作用机制是通过作用其多样性的靶标来实现的,包括破坏细胞膜、作用细胞质成分和干扰代谢等,但部分昆虫抗菌肽的抗菌机制仍未完全明确,深入了解抗菌肽作用机制将推进昆虫抗菌肽药物开发。对已发现的昆虫抗菌肽的作用机制及其应用进行了综述。     

细菌纤维素/氧化亚铜膜的抗菌性能及机制研究

采用抗菌试验来表征不同配方的细菌纤维素/氧化亚铜膜的特性,用大肠埃希菌和黑根霉对细菌纤维素/氧化亚铜膜进行定性分析;用大肠埃希菌和金黄色葡萄球菌对细菌纤维素/氧化亚铜膜进行定量分析,得出抑菌率。通过电镜试验,初步观察样品对细菌细胞的破坏机制,试验结果表明:不同配方的细菌纤维素/氧化亚铜膜的抗菌能力不同,抗菌机制主要是改变细胞膜通透性和抑制细胞复制,最终导致细胞死亡。     

海洋生物抗菌肽在美容业的应用研究现状

抗菌肽是一类对真菌、细菌和病毒有广谱抗菌活性的小分子蛋白质。海洋生物依靠体内独特的免疫机制抵抗入侵细菌或病原体,因此內源性抗菌肽丰富,成为开发天然抗菌肽的重要资源。本文综述了海洋生物抗菌肽的研究现状及在美容产品中的应用潜力。海洋生物抗菌肽主要来源于海洋脊椎动物及海洋非脊椎动物。它在作为天然化妆品的防腐剂及治疗痤疮方面应用前景广阔。     

假单胞菌属合成环脂肽分子的研究进展

假单胞菌属合成的环脂肽是一类由脂肪酸和肽链组成、通过酯键成环、具有两亲性的分子。环脂肽有多种生理功能,除具表面活性外,还具有抗细菌、抗病毒、抗真菌、抑制肿瘤细胞等活性,可作为潜在的抗生素类药物被开发。本文就假单胞菌属所合成环脂肽的种类、功能和生物合成机制进行总结,同时对分子生物学、生物信息学等新兴学科技术结合传统分离鉴定技术在发现新型环脂肽类物质方面的运用作一综述。     

抗菌肽的结构修饰及活性研究进展

抗生素耐药性是目前急需解决的医疗问题之一,寻找新的有效抗菌药物是解决耐药性的一种有效途径。抗菌肽(Antimicrobial peptides, AMPs)是广泛存在于生物体内的一类重要的多肽活性物质,具有广谱抗菌活性,并且部分抗菌肽还具有一定的抗肿瘤活性。因为抗菌肽具有独特的破膜作用机制,传统的耐药机制难以对其产生影响,在治疗细菌感染方面有广阔的应用前景,因此得到了研究者的广泛关注。主要通过总结相关研究文献,对抗菌肽的研究现状以及结构改造的研究加以综述,为抗菌肽在临床上的进一步研究和开发提供参考。     

Antimicrobial Polymer−Based Assemblies: A Review

An antimicrobial supramolecular assembly (ASA) is conspicuous in biomedical applications. Among the alternatives to overcome microbial resistance to antibiotics and drugs, ASAs, including antimicrobial peptides (AMPs) and polymers (APs), provide formulations with optimal antimicrobial activity and acceptable toxicity. AMPs and APs have been delivered by a variety of carriers such as nanoparticles, coatings, multilayers, hydrogels, liposomes, nanodisks, lyotropic lipid phases, nanostructured lipid carriers, etc. They have similar mechanisms of action involving adsorption to the cell wall, penetration across the cell membrane, and microbe lysis. APs, however, offer the advantage of cheap synthetic procedures, chemical stability, and improved adsorption (due to multipoint attachment to microbes), as compared to the expensive synthetic routes, poor yield, and subpar in vivo stability seen in AMPs. We review recent advances in polymer−based antimicrobial assemblies involving AMPs and APs.     

Development of Bactericidal Peptides against Multidrug-Resistant Acinetobacter baumannii with Enhanced Stability and Low Toxicity

Pathogenic superbugs are the root cause of untreatable complex infections with limited or no treatment options. These infections are becoming more common as clinical antibiotics have lost their effectiveness over time. Therefore, the development of novel antibacterial agents is urgently needed to counter these microbes. Antimicrobial peptides (AMPs) are a viable treatment option due to their bactericidal potency against multiple microbial classes. AMPs are naturally selected physiological microbicidal agents that are found in all forms of organisms. In the present study, we developed two tilapia piscidin 2 (TP2)-based AMPs for antimicrobial application. Unlike the parent peptide, the redesigned peptides showed significant antimicrobial activity against multidrug-resistant bacterial species. These peptides also showed minimal cytotoxicity. In addition, they were significantly active in the presence of physiological salts, 50% human serum and elevated temperature. The designed peptides also showed synergistic activity when combined with clinical antibiotics. The current approach demonstrates a fruitful strategy for developing potential AMPs for antimicrobial application. Such AMPs have potential for progression to further trials and drug development investigations.     

Effect of Secondary Structure and Side Chain Length of Hydrophobic Amino Acid Residues on the Antimicrobial Activity and Toxicity of 14-Residue-Long de novo AMPs

Herein we report the efficacy and toxicity of three de novo designed cationic antimicrobial peptides (AMPs) LL-14, VV-14 and ββ-14, where side chains of the hydrophobic amino acids were reduced gradually. The AMPs showed broad-spectrum antimicrobial activity against three pathogens from the ESKAPE group and two fungal strains. This study showed that side chains which are either too long or too short increase toxicity and lower antimicrobial activity, respectively. VV-14 was found to be non-cytotoxic and highly potent under physiological salt concentrations against several pathogens, especially Salmonella typhi TY2. These AMPs acted via membrane deformation, depolarization, and lysis. The activity of the AMPs is related to their ability to take on amphipathic helical conformations in the presence of microbial membrane mimics. Among AMPs with the same charge, hydrophobic interactions between the side chains of the residues with cell membrane lipids determine their antimicrobial potency and cytotoxicity. Strikingly, an optimum hydrophobic interaction is the crux of generating highly potent non-cytotoxic AMPs.     

Short Antimicrobial Lipo‐α/γ‐AA Hybrid Peptides

The last two decades have seen the rise of antimicrobial peptides (AMPs) to combat emerging antibiotic resistance. Herein we report the solid‐phase synthesis of short lipidated α/γ‐AA hybrid peptides. This family of lipo‐chimeric peptidomimetics displays potent and broad‐spectrum antimicrobial activity against a range of multi‐drug resistant Gram‐positive and Gram‐negative bacteria. These lipo‐α/γ‐AA hybrid peptides also demonstrate high biological specificity, with no hemolytic activity towards red blood cells. Fluorescence microscopy suggests that these lipo‐α/γ‐AA chimeric peptides can mimic the mode of action of AMPs and kill bacterial pathogens via membrane disintegration. As the composition of these chimeric peptides is simple, therapeutic development could be economically feasible and amenable for a variety of antimicrobial applications.     

Is It Possible to Create Antimicrobial Peptides Based on the Amyloidogenic Sequence of Ribosomal S1 Protein of P. aeruginosa?

The development and testing of new antimicrobial peptides (AMPs) represent an important milestone toward the development of new antimicrobial drugs that can inhibit the growth of pathogens and multidrug-resistant microorganisms such as Pseudomonas aeruginosa, Gram-negative bacteria. Most AMPs achieve these goals through mechanisms that disrupt the normal permeability of the cell membrane, which ultimately leads to the death of the pathogenic cell. Here, we developed a unique combination of a membrane penetrating peptide and peptides prone to amyloidogenesis to create hybrid peptide: “cell penetrating peptide + linker + amyloidogenic peptide”. We evaluated the antimicrobial effects of two peptides that were developed from sequences with different propensities for amyloid formation. Among the two hybrid peptides, one was found with antibacterial activity comparable to antibiotic gentamicin sulfate. Our peptides showed no toxicity to eukaryotic cells. In addition, we evaluated the effect on the antimicrobial properties of amino acid substitutions in the non-amyloidogenic region of peptides. We compared the results with data on the predicted secondary structure, hydrophobicity, and antimicrobial properties of the original and modified peptides. In conclusion, our study demonstrates the promise of hybrid peptides based on amyloidogenic regions of the ribosomal S1 protein for the development of new antimicrobial drugs against P. aeruginosa.     

Structure and Formation Mechanism of Antimicrobial Peptides Temporin B- and L-Induced Tubular Membrane Protrusion

Temporins are a family of antimicrobial peptides (AMPs) isolated from frog skin, which are very short, weakly charged, and highly hydrophobic. They execute bactericidal activities in different ways from many other AMPs. This work investigated morphological changes of planar bilayer membranes composed of mixed zwitterionic and anionic phospholipids induced by temporin B and L (TB and TL) using all-atom and coarse-grained molecular dynamics simulations. We found that TB and TL fold to α-helices at the membrane surface and penetrate shallowly into the bilayer. These short AMPs have low propensity to induce membrane pore formation but possess high ability to extract lipids out. At relatively high peptide concentrations, the strong hydrophobicity of TB and TL promotes them to aggregate into clusters on the membrane surface. These aggregates attract a large amount of lipids out of the membrane to release compression induced by other dispersed peptides binding to the membrane. The extruded lipids mix evenly with the peptides in the cluster and form tubule-like protrusions. Certain water molecules follow the movement of lipids, which not only fill the cavities of the protrusion but also assist in maintaining the tubular structures. In contrast, the peptide-free leaflet remains intact. The present results unravel distinctive antimicrobial mechanisms of temporins disturbing membranes.     

The Role of Antimicrobial Peptides in Preterm Birth

Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.     

Marine Antimicrobial Peptides: Nature Provides Templates for the Design of Novel Compounds against Pathogenic Bacteria

The discovery of antibiotics for the treatment of bacterial infections brought the idea that bacteria would no longer endanger human health. However, bacterial diseases still represent a worldwide treat. The ability of microorganisms to develop resistance, together with the indiscriminate use of antibiotics, is mainly responsible for this situation; thus, resistance has compelled the scientific community to search for novel therapeutics. In this scenario, antimicrobial peptides (AMPs) provide a promising strategy against a wide array of pathogenic microorganisms, being able to act directly as antimicrobial agents but also being important regulators of the innate immune system. This review is an attempt to explore marine AMPs as a rich source of molecules with antimicrobial activity. In fact, the sea is poorly explored in terms of AMPs, but it represents a resource with plentiful antibacterial agents performing their role in a harsh environment. For the application of AMPs in the medical field limitations correlated to their peptide nature, their inactivation by environmental pH, presence of salts, proteases, or other components have to be solved. Thus, these peptides may act as templates for the design of more potent and less toxic compounds.     

Manipulating Active Structure and Function of Cationic Antimicrobial Peptide CM15 with the Polysulfonated Drug Suramin: A Step Closer to in Vivo Complexity

Antimicrobial peptides (AMPs) kill bacteria by targeting their membranes through various mechanisms involving peptide assembly, often coupled with disorder-to-order structural transition. However, for several AMPs, similar conformational changes in cases in which small organic compounds of both endogenous and exogenous origin have induced folded peptide conformations have recently been reported. Thus, the function of AMPs and of natural host defence peptides can be significantly affected by the local complex molecular environment in vivo; nonetheless, this area is hardly explored. To address the relevance of such interactions with regard to structure and function, we have tested the effects of the therapeutic drug suramin on the membrane activity and antibacterial efficiency of CM15, a potent hybrid AMP. The results provided insight into a dynamic system in which peptide interaction with lipid bilayers is interfered with by the competitive binding of CM15 to suramin, resulting in an equilibrium dependent on peptide-to-drug ratio and vesicle surface charge. In vitro bacterial tests showed that when CM15 ⋅ suramin complex formation dominates over membrane binding, antimicrobial activity is abolished. On the basis of this case study, it is proposed that small-molecule secondary structure regulators can modify AMP function and that this should be considered and could potentially be exploited in future development of AMP-based antimicrobial agents.