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负载镓(III)和铁(III)的多糖对金黄色葡萄球菌、大肠杆菌和白色念珠菌体外生长的抗菌特性

Antimicrobial Properties of Gallium(III)- and Iron(III)-Loaded Polysaccharides Affecting the Growth of , and , In Vitro.

作者信息

Best Mark G, Cunha-Reis Cassilda, Ganin Alexey Y, Sousa Aureliana, Johnston Jenna, Oliveira Ana L, Smith David G E, Yiu Humphrey H P, Cooper Ian R

机构信息

School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, U.K.

CBQF-Centro de Biotecnologia e Química Fina Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, R. de Diogo Botelho 1327, 4169-005 Porto, Portugal.

出版信息

ACS Appl Bio Mater. 2020 Nov 16;3(11):7589-7597. doi: 10.1021/acsabm.0c00811. Epub 2020 Oct 12.

Abstract

Antimicrobial resistance (AMR) has become a global concern as many bacterial species have developed resistance to commonly prescribed antibiotics, making them ineffective to treatments. One type of antibiotics, gallium(III) compounds, stands out as possible candidates due to their unique "Trojan horse" mechanism to tackle bacterial growth, by substituting iron(III) in the metabolic cycles of bacteria. In this study, we tested three polysaccharides (carboxymethyl cellulose (CMC), alginate, and pectin) as the binding and delivery agent for gallium on three bacteria (, and ) with a potential bioresponsive delivery mode. Two types of analysis on bacterial growth (minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC)) were carried out while iron(III)-loaded polysaccharide samples were also tested for comparison. The results suggested that gallium showed an improved inhibitory activity on bacterial growth, in particular gallium(III)-loaded carboxymethyl cellulose (Ga-CMC) sample showing an inhibiting effect on growth for all three tested bacteria. At the MIC for all three bacteria, Ga-CMC showed no cytotoxicity effect on human dermal neonatal fibroblasts (HDNF). Therefore, these bioresponsive gallium(III) polysaccharide compounds show significant potential to be developed as the next-generation antibacterial agents with controlled release capability.

摘要

由于许多细菌物种已对常用抗生素产生耐药性,使这些抗生素在治疗中失效,抗菌耐药性(AMR)已成为全球关注的问题。一类抗生素,镓(III)化合物,因其独特的“特洛伊木马”机制而脱颖而出,有望成为候选药物,该机制通过在细菌代谢循环中取代铁(III)来抑制细菌生长。在本研究中,我们测试了三种多糖(羧甲基纤维素(CMC)、藻酸盐和果胶)作为镓的结合和递送剂,用于三种细菌(、和),采用潜在的生物响应递送模式。对细菌生长进行了两种分析(最低抑菌浓度(MIC)和最低杀菌浓度(MBC)),同时还测试了负载铁(III)的多糖样品以作比较。结果表明,镓对细菌生长的抑制活性有所提高,特别是负载镓(III)的羧甲基纤维素(Ga-CMC)样品对所有三种测试细菌的生长均有抑制作用。在所有三种细菌的MIC浓度下,Ga-CMC对人皮肤新生儿成纤维细胞(HDNF)无细胞毒性作用。因此,这些具有生物响应性的镓(III)多糖化合物具有作为具有控释能力的下一代抗菌剂开发的巨大潜力。

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