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研究塞拉菌素对 的有效性,以开发新的抗菌和抗黏附策略。

Investigating the Effectiveness of Ceragenins against to Develop New Antimicrobial and Anti-Adhesive Strategies.

机构信息

Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Białystok, 15-222 Białystok, Poland.

Independent Laboratory of Nanomedicine, Medical University of Białystok, 15-222 Białystok, Poland.

出版信息

Int J Mol Sci. 2024 Jun 27;25(13):7036. doi: 10.3390/ijms25137036.

Abstract

A growing body of experimental data indicates that ceragenins (CSAs), which mimic the physicochemical properties of the host's cationic antimicrobial peptide, hold promise for the development of a new group of broad-spectrum antimicrobials. Here, using a set of in vivo experiments, we assessed the potential of ceragenins in the eradication of an important etiological agent of nosocomial infections, . Assessment of the bactericidal effect of ceragenins CSA-13, CSA-44, and CSA-131 on clinical isolates of ( = 65) and their effectiveness against bacterial cells embedded in the biofilm matrix after biofilm growth on abiotic surfaces showed a strong bactericidal effect of the tested molecules regardless of bacterial growth pattern. AFM assessment of bacterial cell topography, bacterial cell stiffness, and adhesion showed significant membrane breakdown and rheological changes, indicating the ability of ceragenins to target surface structures of cells. In the cell culture of A549 lung epithelial cells, ceragenin CSA-13 had the ability to inhibit bacterial adhesion to host cells, suggesting that it interferes with the mechanism of bacterial cell invasion. These findings highlight the potential of ceragenins as therapeutic agents in the development of antimicrobial strategies against bacterial infections caused by .

摘要

越来越多的实验数据表明,模拟宿主阳离子抗菌肽理化特性的杀菌素(CSAs)有望成为一类新的广谱抗菌药物。在这里,我们通过一系列体内实验评估了杀菌素在消除医院感染重要病原体 ( = 65)方面的潜力及其对非生物表面生物膜生长后嵌入生物膜基质中的细菌细胞的有效性。对临床分离株的杀菌素 CSA-13、CSA-44 和 CSA-131 的杀菌效果的评估表明,无论细菌生长模式如何,这些测试分子都具有很强的杀菌作用。原子力显微镜(AFM)评估细菌细胞形貌、细菌细胞刚性和黏附性表明,细胞膜明显破裂和流变学发生变化,这表明杀菌素有靶向 细胞表面结构的能力。在 A549 肺上皮细胞的细胞培养中,杀菌素 CSA-13 具有抑制细菌黏附宿主细胞的能力,这表明它干扰了细菌细胞入侵的机制。这些发现强调了杀菌素作为治疗剂在开发针对 引起的细菌感染的抗菌策略方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e2/11241064/7a950572102a/ijms-25-07036-g001.jpg

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