Pachón-Ibáñez María Eugenia, Smani Younes, Pachón Jerónimo, Sánchez-Céspedes Javier
Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville.
Department of Medicine, University of Seville, Seville, Spain.
FEMS Microbiol Rev. 2017 May 1;41(3):323-342. doi: 10.1093/femsre/fux012.
Infectious diseases caused by bacteria, viruses or fungi are among the leading causes of death worldwide. The emergence of drug-resistance mechanisms, especially among bacteria, threatens the efficacy of all current antimicrobial agents, some of them already ineffective. As a result, there is an urgent need for new antimicrobial drugs. Host defense antimicrobial peptides (HDPs) are natural occurring and well-conserved peptides of innate immunity, broadly active against Gram-negative and Gram-positive bacteria, viruses and fungi. They also are able to exert immunomodulatory and adjuvant functions by acting as chemotactic for immune cells, and inducing cytokines and chemokines secretion. Moreover, they show low propensity to elicit microbial adaptation, probably because of their non-specific mechanism of action, and are able to neutralize exotoxins and endotoxins. HDPs have the potential to be a great source of novel antimicrobial agents. The goal of this review is to provide an overview of the advances made in the development of human defensins as well as the cathelicidin LL-37 and their derivatives as antimicrobial agents against bacteria, viruses and fungi for clinical use.
由细菌、病毒或真菌引起的传染病是全球主要死因之一。耐药机制的出现，尤其是在细菌中，威胁着所有现有抗菌药物的疗效，其中一些药物已经失效。因此，迫切需要新的抗菌药物。宿主防御抗菌肽（HDPs）是天然存在且高度保守的先天免疫肽，对革兰氏阴性菌和革兰氏阳性菌、病毒及真菌具有广泛活性。它们还能够通过作为免疫细胞的趋化剂以及诱导细胞因子和趋化因子分泌来发挥免疫调节和佐剂功能。此外，它们引发微生物适应性的倾向较低，这可能是由于其非特异性作用机制，并且能够中和外毒素和内毒素。HDPs有潜力成为新型抗菌药物的重要来源。本综述的目的是概述人类防御素以及杀菌肽LL-37及其衍生物作为抗细菌、病毒和真菌的临床用抗菌剂在开发方面取得的进展。
