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硬骨鱼抗菌肽——来自海洋资源的天然肽类抗生素的计算机模拟视角

Teleost Piscidins-In Silico Perspective of Natural Peptide Antibiotics from Marine Sources.

作者信息

Asensio-Calavia Patricia, González-Acosta Sergio, Otazo-Pérez Andrea, López Manuel R, Morales-delaNuez Antonio, Pérez de la Lastra José Manuel

机构信息

Biotechnology of Macromolecules Research Group, Instituto de Productos Naturales y Agrobiología (IPNA-CSIC), Avda. Astrofísico Francisco Sánchez, 3, 38206 San Cristóbal de La Laguna, Spain.

School of Doctoral and Graduate Studies, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez, SN. Edificio Calabaza-Apdo. 456, 38200 San Cristóbal de La Laguna, Spain.

出版信息

Antibiotics (Basel). 2023 May 5;12(5):855. doi: 10.3390/antibiotics12050855.

Abstract

Fish, like all other animals, are exposed to constant contact with microbes, both on their skin and on the surfaces of their respiratory and digestive systems. Fish have a system of non-specific immune responses that provides them with initial protection against infection and allows them to survive under normal conditions despite the presence of these potential invaders. However, fish are less protected against invading diseases than other marine vertebrates because their epidermal surface, composed primarily of living cells, lacks the keratinized skin that serves as an efficient natural barrier in other marine vertebrates. Antimicrobial peptides (AMPs) are one type of innate immune protection present in all life forms. AMPs have been shown to have a broader range of biological effects than conventional antibiotics, including antibacterial, antiviral, antiprotozoal, and antifungal effects. Although other AMPs, such as defensins and hepcidins, are found in all vertebrates and are relatively well conserved, piscidins are found exclusively in Teleost fish and are not found in any other animal. Therefore, there is less information on the expression and bioactivity of piscidins than on other AMPs. Piscidins are highly effective against Gram-positive and Gram-negative bacteria that cause disease in fish and humans and have the potential to be used as pharmacological anti-infectives in biomedicine and aquaculture. To better understand the potential benefits and limitations of using these peptides as therapeutic agents, we are conducting a comprehensive study of the Teleost piscidins included in the "reviewed" category of the UniProt database using bioinformatics tools. They all have amphipathic alpha-helical structures. The amphipathic architecture of piscidin peptides and positively charged residues influence their antibacterial activity. These alpha-helices are intriguing antimicrobial drugs due to their stability in high-salt and metal environments. New treatments for multidrug-resistant bacteria, cancer, and inflammation may be inspired by piscidin peptides.

摘要

与所有其他动物一样,鱼类的皮肤以及呼吸和消化系统表面会不断接触微生物。鱼类拥有一套非特异性免疫反应系统,该系统为它们提供了抵御感染的初始保护,使它们在这些潜在入侵者存在的情况下仍能在正常条件下生存。然而,与其他海洋脊椎动物相比,鱼类抵御入侵疾病的能力较弱,因为其主要由活细胞组成的表皮表面缺乏角质化皮肤,而角质化皮肤在其他海洋脊椎动物中是一种有效的天然屏障。抗菌肽(AMPs)是所有生命形式中存在的一种先天性免疫保护物质。已证明AMPs具有比传统抗生素更广泛的生物学效应,包括抗菌、抗病毒、抗原生动物和抗真菌效应。尽管其他AMPs,如防御素和铁调素,在所有脊椎动物中都有发现且相对保守,但鱼杀菌肽仅在硬骨鱼中发现,在其他任何动物中都未发现。因此,关于鱼杀菌肽的表达和生物活性的信息比其他AMPs要少。鱼杀菌肽对导致鱼类和人类疾病的革兰氏阳性菌和革兰氏阴性菌具有高效性,并且有潜力在生物医学和水产养殖中用作药理学抗感染药物。为了更好地理解将这些肽用作治疗剂的潜在益处和局限性,我们正在使用生物信息学工具对包含在UniProt数据库“已审核”类别的硬骨鱼鱼杀菌肽进行全面研究。它们都具有两亲性α-螺旋结构。鱼杀菌肽的两亲性结构和带正电荷的残基影响其抗菌活性。由于这些α-螺旋在高盐和金属环境中的稳定性,它们是引人关注的抗菌药物。鱼杀菌肽可能会启发针对多重耐药菌、癌症和炎症的新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df4b/10215159/c9e25138fa45/antibiotics-12-00855-g001.jpg

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