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抗菌肽:受进化约束影响的可持续应用

Antimicrobial peptides: Sustainable application informed by evolutionary constraints.

机构信息

College of Chemical Engineering, Fuzhou University, Fuzhou, Fujian 350108, China; College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China.

College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian 350108, China.

出版信息

Biotechnol Adv. 2022 Nov;60:108012. doi: 10.1016/j.biotechadv.2022.108012. Epub 2022 Jun 23.

DOI:10.1016/j.biotechadv.2022.108012
PMID:35752270
Abstract

The proliferation and global expansion of multidrug-resistant (MDR) bacteria have deepened the need to develop novel antimicrobials. Antimicrobial peptides (AMPs) are regarded as promising antibacterial agents because of their broad-spectrum antibacterial activity and multifaceted mechanisms of action with non-specific targets. However, if AMPs are to be applied sustainably, knowledge of how they induce resistance in pathogenic bacteria must be mastered to avoid repeating the traditional antibiotic resistance mistakes currently faced. Furthermore, the evolutionary constraints on the acquisition of AMP resistance by microorganisms in the natural environment, such as functional compatibility and fitness trade-offs, inform the translational application of AMPs. Consequently, the shortcut to achieve sustainable utilization of AMPs is to uncover the evolutionary constraints of bacteria on AMP resistance in nature and find the tricks to exploit these constraints, such as applying AMP cocktails to minimize the efficacy of selection for resistance or combining nanomaterials to maximize the costs of AMP resistance. Altogether, this review dissects the benefits, challenges, and opportunities of utilizing AMPs against disease-causing bacteria, and highlights the use of AMP cocktails or nanomaterials to proactively address potential AMP resistance crises in the future.

摘要

多药耐药(MDR)细菌的增殖和全球扩张加深了开发新型抗菌药物的必要性。抗菌肽(AMPs)被认为是有前途的抗菌剂,因为它们具有广谱抗菌活性和针对非特异性靶标的多种作用机制。然而,如果要可持续地应用 AMPs,就必须掌握它们如何诱导病原菌产生耐药性的知识,以避免重蹈当前面临的传统抗生素耐药性错误。此外,微生物在自然环境中获得 AMP 抗性的进化限制,如功能兼容性和适应度权衡,为 AMP 的转化应用提供了信息。因此,实现 AMP 可持续利用的捷径是揭示细菌在自然界中对 AMP 抗性的进化限制,并找到利用这些限制的技巧,例如应用 AMP 混合物来最小化选择耐药性的效果,或结合纳米材料来最大化 AMP 抗性的成本。总的来说,这篇综述剖析了利用 AMPs 对抗致病菌的益处、挑战和机遇,并强调了使用 AMP 混合物或纳米材料来积极应对未来潜在的 AMP 耐药性危机。

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