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对多重耐药菌具有可调活性的抗菌有机金属树枝状大分子。

Antimicrobial Organometallic Dendrimers with Tunable Activity against Multidrug-Resistant Bacteria.

作者信息

Abd-El-Aziz Alaa S, Agatemor Christian, Etkin Nola, Overy David P, Lanteigne Martin, McQuillan Katherine, Kerr Russell G

机构信息

Department of Chemistry, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.

Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island , 550 University Avenue, Charlottetown, Prince Edward Island C1A 4P3, Canada.

出版信息

Biomacromolecules. 2015 Nov 9;16(11):3694-703. doi: 10.1021/acs.biomac.5b01207. Epub 2015 Oct 16.

Abstract

Multidrug-resistant pathogens are an increasing threat to public health. In an effort to curb the virulence of these pathogens, new antimicrobial agents are sought. Here we report a new class of antimicrobial organometallic dendrimers with tunable activity against multidrug-resistant Gram-positive bacteria that included methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Mechanistically, these redox-active, cationic organometallic dendrimers induced oxidative stress on bacteria and also disrupted the microbial cell membrane. The minimum inhibitory concentrations, which provide a quantitative measure of the antimicrobial activity of these dendrimers, were in the low micromolar range. AlamarBlue cell viability assay also confirms the antimicrobial activity of these dendrimers. Interestingly, these dendrimers were noncytotoxic to epidermal cell lines and to mammalian red blood cells, making them potential antimicrobial platforms for topical applications.

摘要

多重耐药病原体对公共卫生构成的威胁日益增加。为了抑制这些病原体的毒力,人们正在寻找新的抗菌剂。在此,我们报告了一类新型的抗菌有机金属树枝状大分子,它们对包括耐甲氧西林金黄色葡萄球菌和耐万古霉素粪肠球菌在内的多重耐药革兰氏阳性菌具有可调活性。从机制上讲,这些具有氧化还原活性的阳离子有机金属树枝状大分子会在细菌上诱导氧化应激,还会破坏微生物细胞膜。最低抑菌浓度(它提供了这些树枝状大分子抗菌活性的定量测量)处于低微摩尔范围内。AlamarBlue细胞活力测定也证实了这些树枝状大分子的抗菌活性。有趣的是,这些树枝状大分子对表皮细胞系和哺乳动物红细胞无细胞毒性,使其成为局部应用的潜在抗菌平台。

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