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杀菌素及基于杀菌素的核壳纳米系统作为针对引起医院感染的革兰氏阴性杆菌的新型抗菌剂

Ceragenins and Ceragenin-Based Core-Shell Nanosystems as New Antibacterial Agents against Gram-Negative Rods Causing Nosocomial Infections.

作者信息

Karasiński Maciej, Wnorowska Urszula, Durnaś Bonita, Król Grzegorz, Daniluk Tamara, Skłodowski Karol, Głuszek Katarzyna, Piktel Ewelina, Okła Sławomir, Bucki Robert

机构信息

Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, Mickiewicza 2C, 15-222 Bialystok, Poland.

Department of Microbiology and Immunology, Institute of Medical Science, Collegium Medicum, Jan Kochanowski University in Kielce, IX Wieków Kielc 19A, 25-317 Kielce, Poland.

出版信息

Pathogens. 2023 Nov 13;12(11):1346. doi: 10.3390/pathogens12111346.

Abstract

The growing number of infections caused by multidrug-resistant bacterial strains, limited treatment options, multi-species infections, high toxicity of the antibiotics used, and an increase in treatment costs are major challenges for modern medicine. To remedy this, scientists are looking for new antibiotics and treatment methods that will effectively eradicate bacteria while continually developing different resistance mechanisms. Ceragenins are a new group of antimicrobial agents synthesized based on molecular patterns that define the mechanism of antibacterial action of natural antibacterial peptides and steroid-polyamine conjugates such as squalamine. Since ceragenins have a broad spectrum of antimicrobial activity, with little recorded ability of bacteria to develop a resistance mechanism that can bridge their mechanism of action, there are high hopes that this group of molecules can give rise to a new family of drugs effective against bacteria resistant to currently used antibiotics. Experimental data suggests that core-shell nanosystems, in which ceragenins are presented to bacterial cells on metallic nanoparticles, may increase their antimicrobial potential and reduce their toxicity. However, studies should be conducted, among others, to assess potential long-term cytotoxicity and in vivo studies to confirm their activity and stability in animal models. Here, we summarized the current knowledge on ceragenins and ceragenin-containing nanoantibiotics as potential new tools against emerging Gram-negative rods associated with nosocomial infections.

摘要

多重耐药菌株引起的感染数量不断增加、治疗选择有限、多物种感染、所用抗生素毒性高以及治疗成本上升,是现代医学面临的主要挑战。为了补救这一情况,科学家们正在寻找新的抗生素和治疗方法,以有效根除细菌,同时细菌不断产生不同的耐药机制。杀菌肽是一类新的抗菌剂,其合成基于定义天然抗菌肽和类固醇 - 多胺缀合物(如鲨胺)抗菌作用机制的分子模式。由于杀菌肽具有广泛的抗菌活性,几乎没有记录表明细菌能够产生一种能够跨越其作用机制的耐药机制,因此人们对这组分子寄予厚望,希望它们能产生一类新的药物,有效对抗对目前使用的抗生素耐药的细菌。实验数据表明,核壳纳米系统(其中杀菌肽在金属纳米颗粒上呈现给细菌细胞)可能会增加其抗菌潜力并降低其毒性。然而,尤其应该进行研究以评估潜在的长期细胞毒性,并进行体内研究以确认它们在动物模型中的活性和稳定性。在此,我们总结了关于杀菌肽和含杀菌肽的纳米抗生素的现有知识,它们是对抗与医院感染相关的新兴革兰氏阴性杆菌的潜在新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ebe/10674730/75807e9d7db9/pathogens-12-01346-g001.jpg

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