Gandhi Institute of Technology and Management, Gandhi Nagar, Rushikonda, Visakhapatnam, Andhra Pradesh 530045, India; Molecular Medicine, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India; Biotide Solutions LLP, B-23, Geetanjali Enclave, Malviya Nagar, New Delhi 110017, India.
Adv Colloid Interface Sci. 2024 Nov;333:103282. doi: 10.1016/j.cis.2024.103282. Epub 2024 Sep 6.
In recent years, multidrug-resistant pathogenic microorganisms (MDROs) have emerged as a severe threat to human health, exhibiting robust resistance to traditional antibiotics. This has created a formidable challenge in modern medicine as we grapple with limited options to combat these resilient bacteria. Despite extensive efforts by scientists to develop new antibiotics targeting these pathogens, the quest for novel antibacterial molecules has become increasingly arduous. Fortunately, nature offers a potential solution in the form of cationic antimicrobial peptides (AMPs) and their synthetic counterparts. AMPs, naturally occurring peptides, have displayed promising efficacy in fighting bacterial infections by disrupting bacterial cell membranes, hindering their survival and reproduction. These peptides, along with their synthetic mimics, present an exciting alternative in combating antibiotic resistance. They hold the potential to emerge as a formidable tool against MDROs, offering hope for improved strategies to protect communities. Extensive research has explored the diversity, history, and structure-properties relationship of AMPs, investigating their amphiphilic nature for membrane disruption and mechanisms of action. However, despite their therapeutic promise, AMPs face several documented limitations. Among these challenges, poor pharmacokinetic properties stand out, impeding the attainment of therapeutic levels in the body. Additionally, some AMPs exhibit toxicity and susceptibility to protease cleavage, leading to a short half-life and reduced efficacy in animal models. These limitations pose obstacles in developing effective treatments based on AMPs. Furthermore, the high manufacturing costs associated with AMPs could significantly hinder their widespread use. In this review, we aim to present experimental and theoretical insights into different AMPs, focusing specifically on antibacterial peptides (ABPs). Our goal is to offer a concise overview of peptide-based drug candidates, drawing from a wide array of literature and peer-reviewed studies. We also explore recent advancements in AMP development and discuss the challenges researchers face in moving these molecules towards clinical trials. Our main objective is to offer a comprehensive overview of current AMP and ABP research to guide the development of more precise and effective therapies for bacterial infections.
近年来，多药耐药性病原菌（MDROs）对人类健康构成了严重威胁，它们对传统抗生素具有强大的耐药性。这在现代医学中带来了巨大的挑战，因为我们对抗这些具有弹性的细菌的选择有限。尽管科学家们付出了巨大努力来开发针对这些病原体的新型抗生素，但寻找新的抗菌分子变得越来越困难。幸运的是，自然界为阳离子抗菌肽（AMPs）及其合成类似物提供了一种潜在的解决方案。AMPs 是天然存在的肽，通过破坏细菌细胞膜来显示出对抗细菌感染的有希望的功效，从而阻止它们的生存和繁殖。这些肽及其合成类似物在对抗抗生素耐药性方面提供了令人兴奋的替代方案。它们有可能成为对抗 MDROs 的有力工具，为改善保护社区的策略提供了希望。广泛的研究探索了 AMPs 的多样性、历史和结构-性质关系，研究了它们的两亲性质对膜的破坏作用和作用机制。然而，尽管它们具有治疗潜力，但 AMPs 面临着几个有记录的限制。其中，较差的药代动力学特性尤为突出，阻碍了在体内达到治疗水平。此外，一些 AMPs 表现出毒性和对蛋白酶切割的敏感性，导致在动物模型中的半衰期短且功效降低。这些限制在基于 AMPs 开发有效治疗方法方面构成了障碍。此外，与 AMPs 相关的高制造成本可能会严重阻碍它们的广泛使用。在本综述中，我们旨在介绍不同 AMPs 的实验和理论见解，特别关注抗菌肽（ABPs）。我们的目标是提供基于肽的候选药物的简明概述，参考广泛的文献和同行评审的研究。我们还探讨了 AMP 开发的最新进展，并讨论了研究人员在将这些分子推向临床试验时面临的挑战。我们的主要目标是提供对当前 AMP 和 ABP 研究的全面概述，以指导针对细菌感染的更精确和有效的治疗方法的开发。
