阳离子多糖缀合物作为抗生素佐剂使多重耐药细菌重新敏感并预防耐药性,Advanced Materials

当前位置： X-MOL 学术 › Adv. Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

阳离子多糖缀合物作为抗生素佐剂使多重耐药细菌重新敏感并预防耐药性
Advanced Materials ( IF 27.4 ) Pub Date : 2022-08-13 , DOI: 10.1002/adma.202204065
Shaowei Mu ₁ , Yiwen Zhu ₁ , Yu Wang ₁ , Shuang Qu ₁ , Yichun Huang ₁ , Liang Zheng ₁ , Shun Duan ₁ , Bingran Yu ₁ , Meng Qin ₁ , Fu-Jian Xu ₁

Affiliation

近年来，由于耐多药（MDR）细菌的出现，传统抗生素的功效迅速减弱，对人类生命和全球医疗保健构成了严重威胁。目前，新抗生素的开发周期无法与持续的耐多药感染危机相匹配。因此，需要新的策略来使 MDR 细菌对现有抗生素重新敏感。在这项研究中，使用二硫键交换合成了新型阳离子多糖缀合物 Dextran - graft -poly(5-(1,2-dithiolan-3-yl) -N- (2-guanidinoethyl)pentanamide) (Dex- g -PSS _n )聚合。至关重要的是，细菌膜和流出泵会被低于抑制浓度的 Dex- g - PSS _30破坏，增强细菌内的利福平 (RIF) 积累并恢复其功效。结合 Dex- g -PSS ₃₀和 RIF 可防止培养超过 30 代的细菌产生耐药性。此外，Dex- g -PSS ₃₀在肺炎诱导的小鼠模型中恢复了 RIF 的有效性，减少了炎症反应，并表现出优异的体内生物吸收和降解能力。作为一种抗生素佐剂，Dex- g -PSS ₃₀为 RIF 针对 MDR 细菌和细菌耐药性提供了一种新的再敏化策略。这项 Dex- g -PSS ₃₀研究为未来的 MDR 应用提供了坚实的平台。

"点击查看英文标题和摘要"

Cationic Polysaccharide Conjugates as Antibiotic Adjuvants Resensitize Multidrug-Resistant Bacteria and Prevent Resistance

In recent years, traditional antibiotic efficacy has rapidly diminished due to the advent of multidrug-resistant (MDR) bacteria, which poses severe threat to human life and globalized healthcare. Currently, the development cycle of new antibiotics cannot match the ongoing MDR infection crisis. Therefore, novel strategies are required to resensitize MDR bacteria to existing antibiotics. In this study, novel cationic polysaccharide conjugates Dextran-graft-poly(5-(1,2-dithiolan-3-yl)-N-(2-guanidinoethyl)pentanamide) (Dex-g-PSS_n) is synthesized using disulfide exchange polymerization. Critically, bacterial membranes and efflux pumps are disrupted by a sub-inhibitory concentration of Dex-g-PSS₃₀, which enhances rifampicin (RIF) accumulation inside bacteria and restores its efficacy. Combined Dex-g-PSS₃₀ and RIF prevents bacterial resistance in bacteria cultured over 30 generations. Furthermore, Dex-g-PSS₃₀ restores RIF effectiveness, reduces inflammatory reactions in a pneumonia-induced mouse model, and exhibits excellent in vivo biological absorption and degradation capabilities. As an antibiotic adjuvant, Dex-g-PSS₃₀ provides a novel resensitizing strategy for RIF against MDR bacteria and bacterial resistance. This Dex-g-PSS₃₀ research provides a solid platform for future MDR applications.

更新日期：2022-08-13

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>