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抗生素后时代微生物生物膜的治疗:抗菌肽的预防性和治疗性应用及其通过生物信息学工具进行的设计

Treatment of microbial biofilms in the post-antibiotic era: prophylactic and therapeutic use of antimicrobial peptides and their design by bioinformatics tools.

作者信息

Di Luca Mariagrazia, Maccari Giuseppe, Nifosì Riccardo

机构信息

NEST, Istituto Nanoscienze-CNR and Scuola Normale Superiore, Pisa, Italy.

出版信息

Pathog Dis. 2014 Apr;70(3):257-70. doi: 10.1111/2049-632X.12151. Epub 2014 Mar 7.

Abstract

The treatment for biofilm infections is particularly challenging because bacteria in these conditions become refractory to antibiotic drugs. The reduced effectiveness of current therapies spurs research for the identification of novel molecules endowed with antimicrobial activities and new mechanisms of antibiofilm action. Antimicrobial peptides (AMPs) have been receiving increasing attention as potential therapeutic agents, because they represent a novel class of antibiotics with a wide spectrum of activity and a low rate in inducing bacterial resistance. Over the past decades, a large number of naturally occurring AMPs have been identified or predicted from various organisms as effector molecules of the innate immune system playing a crucial role in the first line of defense. Recent studies have shown the ability of some AMPs to act against microbial biofilms, in particular during early phases of biofilm development. Here, we provide a review of the antimicrobial peptides tested on biofilms, highlighting their advantages and disadvantages for prophylactic and therapeutic applications. In addition, we describe the strategies and methods for de novo design of potentially active AMPs and discuss how informatics and computational tools may be exploited to improve antibiofilm effectiveness.

摘要

生物膜感染的治疗极具挑战性,因为处于这种状态下的细菌会对抗生素产生耐药性。当前治疗方法有效性的降低促使人们开展研究,以鉴定具有抗菌活性的新型分子以及抗生物膜作用的新机制。抗菌肽(AMPs)作为潜在的治疗剂受到越来越多的关注,因为它们代表了一类新型抗生素,具有广泛的活性谱且诱导细菌耐药的比率较低。在过去几十年中,大量天然存在的抗菌肽已从各种生物体中被鉴定或预测出来,作为先天免疫系统的效应分子,在第一道防线中发挥着关键作用。最近的研究表明,一些抗菌肽能够对抗微生物生物膜,尤其是在生物膜形成的早期阶段。在此,我们综述了针对生物膜进行测试的抗菌肽,突出了它们在预防性和治疗性应用中的优缺点。此外,我们描述了潜在活性抗菌肽的从头设计策略和方法,并讨论了如何利用信息学和计算工具来提高抗生物膜效果。

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