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新型银纳米粒子-抗生素联合制剂作为有前途的抗菌和抗生物膜候选物,可对抗多种抗生素耐药的 ESKAPE 微生物。

Novel silver nanoparticle-antibiotic combinations as promising antibacterial and anti-biofilm candidates against multiple-antibiotic resistant ESKAPE microorganisms.

机构信息

Antimicrobial Research (AMR) Lab, Department of Biotechnology, University of Mumbai, Vidyanagari, Santacruz (East), Mumbai, Maharashtra 400098, India.

Molecular Biology Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.

出版信息

Colloids Surf B Biointerfaces. 2024 Apr;236:113826. doi: 10.1016/j.colsurfb.2024.113826. Epub 2024 Feb 25.

DOI:10.1016/j.colsurfb.2024.113826
PMID:38447448
Abstract

HYPOTHESIS

The emergence of Multiple Antibiotic Resistance (MAR) in ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens is a global challenge to public health. The inherent antimicrobial nature of silver nanoparticles (AgNPs) makes them promising antimicrobial candidates against antibiotic-resistant pathogens. This study explores the combination of AgNPs with antibiotics (SACs) to create new antimicrobial agents effective against MAR ESKAPE microorganisms.

METHODS

AgNPs were synthesized using Streptococcus pneumoniae ATCC 49619 and characterized for structure and surface properties. The SACs were tested against ESKAPE microorganisms using growth kinetics and time-kill curve methods. The effect of SACs on bacterial biofilms and the disruption of cell membranes was determined. The in-vitro cytotoxicity effect of the AgNPs was also studied.

FINDINGS

The synthesized AgNPs (spherical, 7.37±4.55 nm diameter) were antimicrobial against MAR ESKAPE microorganisms. The SACs showed synergy with multiple conventional antibiotics, reducing their antibacterial concentrations up to 32-fold. Growth kinetics and time-kill studies confirmed the growth retardation effect and bactericidal activity of SACs. Mechanistic studies suggested that these biofilm-eradicating SACs probably resulted in the loss of bacterial cell membrane integrity, leading to leakage of the cytoplasmic content. The AgNPs were highly cytotoxic against skin melanoma cells but non-cytotoxic to normal Vero cells.

摘要

假设

ESKAPE(屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌属)病原体出现的多重抗生素耐药性(MAR)是对全球公共健康的挑战。银纳米粒子(AgNPs)固有的抗菌性质使它们成为有前途的抗抗生素耐药性病原体的抗菌候选物。本研究探讨了将 AgNPs 与抗生素(SACs)联合使用,以创造针对 MAR ESKAPE 微生物的新型抗菌剂。

方法

使用肺炎链球菌 ATCC 49619 合成 AgNPs,并对其结构和表面特性进行表征。使用生长动力学和时间杀伤曲线方法测试 SACs 对 ESKAPE 微生物的作用。测定 SACs 对细菌生物膜的影响和细胞膜的破坏。还研究了 AgNPs 的体外细胞毒性作用。

结果

合成的 AgNPs(球形,直径为 7.37±4.55nm)对 MAR ESKAPE 微生物具有抗菌作用。SACs 与多种常规抗生素表现出协同作用,将其抗菌浓度降低了 32 倍。生长动力学和时间杀伤研究证实了 SACs 的生长抑制作用和杀菌活性。机制研究表明,这些具有生物膜清除作用的 SACs 可能导致细菌细胞膜完整性丧失,导致细胞质内容物泄漏。AgNPs 对皮肤黑色素瘤细胞具有高度细胞毒性,但对正常 Vero 细胞无细胞毒性。

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