关键词: AMP databases Antibiotic resistance actinobacteria antibiotic discovery antimicrobial peptides genome mining tools

来  源:   DOI:10.1016/j.biochi.2024.06.013

Abstract:
Antibiotic resistance has become one of the most serious threats to human health in recent years. In response to the increasing microbial resistance to the antibiotics currently available, it is imperative to develop new antibiotics or explore new approaches to combat antibiotic resistance. Antimicrobial peptides (AMPs) have shown considerable promise in this regard, as the microbes develop low or no resistance against them. The discovery and development of AMPs still confront numerous obstacles such as finding a target, developing assays, and identifying hits and leads, which are time-consuming processes, making it difficult to reach the market. However, with the advent of genome mining, new antibiotics could be discovered efficiently using tools such as BAGEL, antiSMASH, RODEO, etc., providing hope for better treatment of diseases in the future. Computational methods used in genome mining automatically detect and annotate biosynthetic gene clusters in genomic data, making it a useful tool in natural product discovery. This review aims to shed light on the history, diversity, and mechanisms of action of AMPs and the data on new AMPs identified by traditional as well as genome mining strategies. It further substantiates the various phases of clinical trials for some AMPs, as well as an overview of genome mining databases and tools built expressly for AMP discovery. In light of the recent advancements, it is evident that targeted genome mining stands as a beacon of hope, offering immense potential to expedite the discovery of novel antimicrobials.
摘要:
近年来,抗生素耐药性已成为威胁人类健康的最严重威胁之一。为了应对微生物对目前可用抗生素的耐药性增加,必须开发新的抗生素或探索对抗抗生素耐药性的新方法。抗菌肽(AMPs)在这方面显示出相当大的前景,因为微生物对它们产生低抗性或没有抗性。AMPs的发现和发展仍然面临许多障碍,例如寻找目标,开发化验,识别命中和线索,这是耗时的过程,很难进入市场。然而,随着基因组挖掘的出现,使用BAGEL等工具可以有效地发现新的抗生素,antiSMASH,RODEO,等。,为将来更好地治疗疾病提供希望。基因组挖掘中使用的计算方法自动检测和注释基因组数据中的生物合成基因簇,使其成为天然产品发现的有用工具。这篇评论旨在揭示历史,多样性,和AMP的作用机制以及通过传统和基因组挖掘策略确定的新AMP的数据。它进一步证实了一些AMP临床试验的各个阶段,以及专门为AMP发现而构建的基因组挖掘数据库和工具的概述。鉴于最近的进展,很明显,靶向基因组挖掘是希望的灯塔,提供了巨大的潜力,以加快发现新的抗菌药物。
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