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用于抗生素和疫苗的脂肽佐剂:对抗多重耐药和广泛耐药病原体的未来举措。

Lipopeptide adjuvants for antibiotics and vaccines: the future step in the fight against multidrug-resistant and extensively drug-resistant pathogens.

作者信息

Sebilleau Chloé O, Sucheck Steven J

机构信息

Department of Chemistry and Biochemistry, University of Toledo, Toledo, OH 43606, USA.

出版信息

Explor Drug Sci. 2024;2:203-233. doi: 10.37349/eds.2024.00043. Epub 2024 Apr 29.

Abstract

With the surge of antibiotic resistance in bacteria, the need for a larger arsenal of effective antibiotics and vaccines has drastically increased in the past decades. Antibiotics like vaccines can benefit from significant potentiation when used in combination with adjuvants. Antibiotic adjuvants can allow for gram-positive bacteria (GPB) specific treatments to be used against gram-negative bacteria (GNB) infections, with minimal antimicrobial resistance (AMR). In the case of vaccines, they allow for modulation and increase of the immune response. Lipopeptides are molecules of choice because of their ability to activate specific cell surface receptors, penetrate the outer membrane of GNB, safety and ease of synthesis. This review explores the recent developments in lipopeptide adjuvants for antibiotics and vaccines, providing a roadmap on how to develop adjuvants to efficiently combat AMR. After a brief overview of bacterial resistance, lipopeptide adjuvants for antibiotics and vaccines are discussed, providing insights into stability, sources, and delivery methods. Findings discussed in this review could be applied to the development of safer, more effective adjuvants, that could expand the use or repurpose current antibiotics or improve vaccination results in future clinical trials.

摘要

随着细菌对抗生素耐药性的激增,在过去几十年中,对更多有效抗生素和疫苗的需求急剧增加。与疫苗一样,抗生素与佐剂联合使用时可从显著的增效作用中获益。抗生素佐剂可使针对革兰氏阳性菌(GPB)的特异性治疗用于对抗革兰氏阴性菌(GNB)感染,同时将抗菌耐药性(AMR)降至最低。就疫苗而言,佐剂可调节并增强免疫反应。脂肽因其能够激活特定细胞表面受体、穿透GNB的外膜、安全性高且易于合成而成为首选分子。本综述探讨了用于抗生素和疫苗的脂肽佐剂的最新进展,提供了关于如何开发佐剂以有效对抗AMR的路线图。在简要概述细菌耐药性之后,讨论了用于抗生素和疫苗的脂肽佐剂,深入探讨了其稳定性、来源和递送方法。本综述中讨论的研究结果可应用于开发更安全、更有效的佐剂,这可能会扩大现有抗生素的使用范围或使其用途多样化,或在未来临床试验中改善疫苗接种效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ea/12366752/a3e6d6614991/nihms-2095604-f0031.jpg

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