Guerra Maria Eduarda Souza, Vieira Brenda, Calazans Ana Paula Carvalho Thiers, Destro Giulia Vicente, Melo Karina, Rodrigues Emilly, Waz Natalha Tedeschi, Girardello Raquel, Darrieux Michelle, Converso Thiago Rojas
Laboratório de Biologia Molecular de Microrganismos, Universidade São Francisco, Bragança Paulista, Brazil.
Front Microbiol. 2024 Jun 26;15:1405760. doi: 10.3389/fmicb.2024.1405760. eCollection 2024.
The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability . The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.
在过去几十年中，抗菌药物耐药性惊人地增加，这促使人们寻找控制传染病的替代方法。抗菌肽（AMPs）是一类异质性分子，具有广泛的抗菌、抗病毒和抗真菌作用。它们存在于许多生物体中，包括所有脊椎动物类别，是新型抗菌剂的宝贵来源。抗菌肽的独特性质使微生物更难产生耐药性，而它们的免疫调节特性和靶点多样性增强了其在多种疾病（从自身免疫性疾病到不同类型的癌症）中的转化应用。近年来，大量研究评估了抗菌肽在治疗中的应用，许多研究已进入临床试验阶段。本综述探讨了cathelicidin（一类具有强大抗菌和免疫调节作用的抗菌肽大家族）药用特性的最新进展。来自几种生物体的cathelicidin已在病毒和细菌感染、炎症性疾病及肿瘤的疾病模型中进行了测试，结果令人鼓舞。将纳米材料与活性天然抗菌肽（包括LL-37）以及ceragenins等合成类似物相结合，可创造出具有重大临床前景的创新纳米制剂。然而，仍然存在重要的局限性，例如许多cathelicidin对健康宿主细胞具有毒性且稳定性较低。纳米材料和合成生物学的最新进展可能有助于克服当前的局限性，使cathelicidin能够用于未来的治疗。此外，更好地理解cathelicidin的作用机制及其与其他宿主分子的协同作用，将有助于开发更安全、高效的疗法。
