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新型功能化硒纳米线作为抗生素佐剂,通过多种方式克服多重耐药菌的耐药性。

Novel functionalized selenium nanowires as antibiotic adjuvants in multiple ways to overcome drug resistance of multidrug-resistant bacteria.

机构信息

School of Life Sciences, Anhui Agricultural University, Hefei 230036, China.

School of Life Sciences, Anhui Agricultural University, Hefei 230036, China.

出版信息

Biomater Adv. 2022 Jun;137:212815. doi: 10.1016/j.bioadv.2022.212815. Epub 2022 Apr 22.

Abstract

Methicillin-resistant Staphylococcus (MRS) is a multi-drug resistant bacteria that pose a serious threat to human health. Antibacterial nanomaterials are becoming a promising antibiotic substitute or antibiotic adjuvants. In this work, selenium nanowires were modified with nano‑silver (Ag NPs) with antibacterial activity and [Ru(bpy)dppz] with fluorescent labeling of DNA (SRA), and the antibacterial activity, antibacterial mechanism and biological toxicity of SRA synergistic antibiotics were studied. In vitro, antibacterial results show that SRA (12 μg/mL) improves the antibacterial activity of various antibiotics against resistant bacteria and significantly slows the development of bacterial resistance to antibiotics. Studies on antibacterial mechanisms have shown that SRA synergistic antibiotics destroy drug-resistant bacteria through a combination of physical (physical damage) and chemical pathways (destruction of biofilm, membrane depolarization, cell membrane destruction, adenosine triphosphate consumption and reactive oxygen species production). Transcriptomics analysis found that SRA affects bacterial activity by affecting bacterial biosynthesis, ATP synthesis and biofilm formation. Furthermore, SRA synergistic antibiotics can accelerate wound healing of bacterial infection by reducing the inflammatory response. The toxicity evaluation results show that SRA has extremely low cellular and in vivo toxicity. SRA has the potential of clinical application as multiple antibiotic adjuvants to deal with resistant bacterial infections.

摘要

耐甲氧西林金黄色葡萄球菌(MRS)是一种多药耐药菌,对人类健康构成严重威胁。抗菌纳米材料正成为有前途的抗生素替代品或抗生素佐剂。在这项工作中,用具有抗菌活性的纳米银(Ag NPs)和具有 DNA 荧光标记的[Ru(bpy)dppz]对硒纳米线进行了修饰,并研究了 SRA 协同抗生素的抗菌活性、抗菌机制和生物毒性。体外实验结果表明,SRA(12μg/mL)提高了各种抗生素对耐药菌的抗菌活性,并显著减缓了细菌对抗生素耐药性的发展。抗菌机制研究表明,SRA 协同抗生素通过物理途径(物理损伤)和化学途径(破坏生物膜、膜去极化、细胞膜破坏、三磷酸腺苷消耗和活性氧产生)协同破坏耐药菌。转录组学分析发现,SRA 通过影响细菌的生物合成、三磷酸腺苷合成和生物膜形成来影响细菌的活性。此外,SRA 协同抗生素通过减少炎症反应,加速细菌感染的伤口愈合。毒性评价结果表明,SRA 具有极低的细胞毒性和体内毒性。SRA 作为多种抗生素佐剂,具有应对耐药菌感染的临床应用潜力。

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