Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1.
Curr Pharm Des. 2014;20(5):771-92. doi: 10.2174/13816128113199990011.
Our incessant tug-of-war with multidrug resistant pathogenic bacteria has prompted researchers to explore novel methods of designing therapeutics in order to defend ourselves against infectious diseases. Combined advances in whole genome analysis, bioinformatics algorithms, and biochemical techniques have led to the discovery and subsequent characterization of an abundant array of functional small peptides in microorganisms and multicellular organisms. Typically classified as having 10 to 100 amino acids, many of these peptides have been found to have dual activities, executing important defensive and regulatory functions in their hosts. In higher organisms, such as mammals, plants, and fungi, host defense peptides have been shown to have immunomodulatory and antimicrobial properties. In microbes, certain growth-inhibiting peptides have been linked to the regulation of diverse cellular processes. Examples of these processes include quorum sensing, stress response, cell differentiation, biofilm formation, pathogenesis, and multidrug tolerance. In this review, we will present a comprehensive overview of the discovery, characteristics, and functions of host- and bacteria-derived peptides with antimicrobial activities. The advantages and possible shortcomings of using these peptides as antimicrobial agents and targets will also be discussed. We will further examine current efforts in engineering synthetic peptides to be used as therapeutics and/or drug delivery vehicles.
我们与多药耐药性病原菌无休止的斗争促使研究人员探索新的治疗方法设计,以保护自己免受传染病的侵害。全基因组分析、生物信息学算法和生化技术的综合进步导致了大量功能小肽在微生物和多细胞生物中的发现和随后的特征描述。这些肽通常被分类为具有 10 到 100 个氨基酸,其中许多被发现具有双重活性,在宿主中执行重要的防御和调节功能。在高等生物,如哺乳动物、植物和真菌中,宿主防御肽已被证明具有免疫调节和抗菌特性。在微生物中,某些抑制生长的肽与多种细胞过程的调节有关。这些过程的例子包括群体感应、应激反应、细胞分化、生物膜形成、发病机制和多药耐受。在这篇综述中,我们将全面介绍具有抗菌活性的宿主和细菌来源肽的发现、特性和功能。还将讨论将这些肽用作抗菌剂和靶标的优点和可能的缺点。我们将进一步研究工程合成肽作为治疗剂和/或药物输送载体的应用。