Microbiology Laboratory, School of Pharmacy, Saint Joseph University, Beirut, Lebanon.
College of Natural and Health Sciences, Zayed University, Dubai, United Arab Emirates.
Front Immunol. 2020 Jun 30;11:1198. doi: 10.3389/fimmu.2020.01198. eCollection 2020.
The treatment of respiratory infections is associated with the dissemination of antibiotic resistance in the community and clinical settings. Development of new antibiotics is notoriously costly and slow; therefore, alternative strategies are needed. Antimicrobial peptides (AMPs), the central effector molecules of the immune system, are being considered as alternatives to conventional antibiotics. Most AMPs are epithelium-derived and play a key role in host defense at mucosal surfaces. They are classified on the basis of their structure and amino acid motifs. These peptides display a range of activities, including not only direct antimicrobial activity, but also immunomodulation and wound repair. In the lung, airway epithelial cells and neutrophils, in particular, contribute to AMP synthesis. The relevance of AMPs for host defense against infection has been demonstrated in animal models and is supported by observations in patient studies, showing altered expression and/or unfavorable circumstances for their action in a variety of lung diseases. Of note, AMPs are active against bacterial strains that are resistant to conventional antibiotics, including multidrug-resistant bacteria. Several strategies have been proposed to use these peptides in the treatment of infections, including direct administration of AMPs. In this review, we focus on studies related to direct bactericidal effects of AMPs and their potential clinical applications with a particular focus on cystic fibrosis.
呼吸道感染的治疗与社区和临床环境中抗生素耐药性的传播有关。新型抗生素的开发成本高且速度慢;因此,需要替代策略。抗菌肽(AMPs)是免疫系统的核心效应分子,被认为是传统抗生素的替代品。大多数 AMPs 是上皮细胞衍生的,在黏膜表面的宿主防御中发挥关键作用。它们根据结构和氨基酸基序进行分类。这些肽显示出多种活性,不仅具有直接的抗菌活性,还具有免疫调节和伤口修复作用。在肺部,气道上皮细胞和中性粒细胞特别有助于 AMP 的合成。AMP 对宿主抗感染的相关性已在动物模型中得到证实,并得到了患者研究的支持,这些研究表明,在各种肺部疾病中,其表达发生改变和/或不利于其作用。值得注意的是,AMP 对对抗生素耐药的细菌株(包括多药耐药菌)具有活性。已经提出了几种使用这些肽治疗感染的策略,包括直接给予 AMP。在这篇综述中,我们重点介绍了与 AMP 的直接杀菌作用及其在囊性纤维化中的潜在临床应用相关的研究。