Xiao Bingru, Wang Jie, Xing Jie, He Lulu, Xu Chen, Wu Aiguo, Li Juan
Cixi Biomedical Research Institute, Wenzhou Medical University, Cixi 315300, China.
Laboratory of Advanced Theranostic Materials and Technology, Ningbo Key Laboratory of Biomedical Imaging Probe Materials and Technology, Chinese Academy of Sciences (CAS) Key Laboratory of Magnetic Materials and Devices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo 315201, China.
Bioconjug Chem. 2025 Mar 19;36(3):311-331. doi: 10.1021/acs.bioconjchem.4c00594. Epub 2025 Feb 19.
Bacterial keratitis is a prevalent, and severe corneal illness resulting from bacterial pathogens. Failure to administer a timely and suitable therapy may lead to corneal opacity, ulceration, significant vision impairment, or potential blindness. Current clinical interventions for bacterial keratitis involve the administration of topical antimicrobial agents and systemic antibiotics. However, the misuse and overuse of antibiotics have led to the rapid emergence of antibiotic-resistant bacteria. Additionally, the restricted antibacterial spectrum and possible adverse effects of antibiotics have provided considerable obstacles to traditional therapies. This highlights the urgent need for novel and highly effective antimicrobial agents. Antimicrobial peptides (AMPs) are a class of naturally occurring or synthetically designed small molecules that have gained significant attention due to their unique antimicrobial mechanisms and low risk of resistance development. AMPs exhibit promising potential in treating bacterial keratitis through direct antibacterial mechanisms, such as inhibiting cell wall synthesis, disrupting cell membranes, and interfering with nucleic acid metabolism, as well as indirect mechanisms, including modulation of the host immune response. This review provides a comprehensive overview of the antibacterial mechanisms of AMPs and their advancements in the treatment of bacterial keratitis. It emphasizes the role of various modification strategies and artificial-intelligence-assisted design in enhancing the antibacterial efficacy, stability, and biocompatibility of AMPs. Furthermore, this review discusses the latest progress in combining AMPs with delivery systems for improved therapeutic outcomes. Finally, the review highlights the current challenges and future perspectives of AMPs in bacterial keratitis treatment, providing valuable insights for developing novel AMPs with high antibacterial efficacy, stability, and safety for bacterial keratitis therapies.
细菌性角膜炎是一种由细菌病原体引起的常见且严重的角膜疾病。未能及时给予适当治疗可能导致角膜混浊、溃疡、严重视力损害或潜在失明。目前针对细菌性角膜炎的临床干预措施包括局部使用抗菌剂和全身使用抗生素。然而，抗生素的滥用和过度使用导致了抗生素耐药菌的迅速出现。此外，抗生素有限的抗菌谱和可能的不良反应给传统治疗带来了相当大的障碍。这凸显了对新型高效抗菌剂的迫切需求。抗菌肽（AMPs）是一类天然存在或人工设计的小分子，因其独特的抗菌机制和低耐药风险而备受关注。抗菌肽通过直接抗菌机制（如抑制细胞壁合成、破坏细胞膜和干扰核酸代谢）以及间接机制（包括调节宿主免疫反应）在治疗细菌性角膜炎方面展现出了有前景的潜力。本综述全面概述了抗菌肽的抗菌机制及其在细菌性角膜炎治疗中的进展。它强调了各种修饰策略和人工智能辅助设计在提高抗菌肽的抗菌效果、稳定性和生物相容性方面的作用。此外，本综述讨论了将抗菌肽与递送系统相结合以改善治疗效果的最新进展。最后，该综述突出了抗菌肽在细菌性角膜炎治疗中当前面临的挑战和未来前景，为开发具有高抗菌效果、稳定性和安全性的新型抗菌肽用于细菌性角膜炎治疗提供了有价值的见解。
