Silver nanoparticles enhance the efficacy of aminoglycosides against antibiotic-resistant bacteria

Frontiers in Microbiology

Microbiology

Wren R. Dees¹  Jacob A. Best¹  Autumn S. Dove¹  Dominika I. Dzurny¹  Garrett L. Ellward¹  Daniel M. Czyż¹  Kotaro Fujii²  Nan Qin³  Lauren A. Alt³  Carmen C. Nunez Rodriguez³  Nicholas G. Rudawski⁴ 

[1] Department of Microbiology and Cell Science, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL, United States;Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, United States;Center for NeuroGenetics, University of Florida, Gainesville, FL, United States;Natural Immunogenics Corporation, Sarasota, FL, United States;Research Service Centers, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, United States;

关键词: silver nanoparticles;    antibiotic resistance;    Caenorhabditis elegans;    antimicrobials;    synergism;    antibiotic potentiators;    aminoglycosides;   

DOI  :  10.3389/fmicb.2022.1064095

 received in 2022-10-07, accepted in 2022-12-30,  发布年份 2023

来源: Frontiers

【 摘 要 】

As the threat of antimicrobial-resistant bacteria compromises the safety and efficacy of modern healthcare practices, the search for effective treatments is more urgent than ever. For centuries, silver (Ag) has been known to have antibacterial properties and, over the past two decades, Ag-based nanoparticles have gained traction as potential antimicrobials. The antibacterial efficacy of Ag varies with structure, size, and concentration. In the present study, we examined Ag nanoparticles (AgNPs) for their antimicrobial activity and safety. We compared different commercially-available AgNPs against gram-negative Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and gram-positive Staphylococcus aureus methicillin-resistant and susceptible strains. The most effective formula of AgNPs tested had single-digit (μg/mL) minimum inhibitory concentrations against gram-negative multidrug-resistant clinical bacterial isolates with novel and emerging mechanisms of resistance. The mode of killing was assessed in E. coli and was found to be bactericidal, which is consistent with previous studies using other AgNP formulations. We evaluated cytotoxicity by measuring physiological readouts using the Caenorhabditis elegans model and found that motility was affected, but not the lifespan. Furthermore, we found that at their antibacterial concentrations, AgNPs were non-cytotoxic to any of the mammalian cell lines tested, including macrophages, stem cells, and epithelial cells. More interestingly, our experiments revealed synergy with clinically relevant antibiotics. We found that a non-toxic and non-effective concentration of AgNPs reduced the minimum inhibitory concentrations of aminoglycoside by approximately 22-fold. Because both aminoglycosides and Ag are known to target the bacterial ribosome, we tested whether Ag could also target eukaryotic ribosomes. We measured the rate of mistranslation at bactericidal concentration and found no effect, indicating that AgNPs are not proteotoxic to the host at the tested concentrations. Collectively, our results suggest that AgNPs could have a promising clinical application as a potential stand-alone therapy or antibiotic adjuvants.

【 授权许可】

Unknown   
Copyright © 2023 Dove, Dzurny, Dees, Qin, Nunez Rodriguez, Alt, Ellward, Best, Rudawski, Fujii and Czyż.