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

Abstract

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.

Antimicrobial and Antiproliferative Activity of Green Synthesized Silver Nanoparticles Using Bee Bread Extracts

“…Another study reported that AgNPs were effective against CRAB and could inhibit biofilm formation, a major contributor to antibiotic resistance [ 69 ]. AgNPs have also been shown to enhance the activity of conventional antibiotics, making them more effective against antibiotic-resistant bacteria such as E. coli [ 89 ]. Despite the promising antimicrobial activity of AgNPs, the development and application of these nanoparticles as antimicrobial agents still face some challenges, such as the potential for toxicity to plants, animals, and human cells; for this reason, a comprehensive toxicological evaluation is necessary [ 18 ].…”

An Electroconductive and Antibacterial Adhesive Nanocomposite Hydrogel for High‐Performance Skin Wound Healing

“…Separately, PVA, CD, and AgNPs at suitable concentrations are known to be non-toxic for different animal cells. [83][84][85] As an atypical macromolecule, HAG's cytocompatibility has never been examined before. Pure HAG at low to moderate concentrations was biocompatible and even promoted cell growth (Figure S7, Supporting Information).…”

Exploring the efficacy of tryptone-stabilized silver nanoparticles against respiratory tract infection-causing bacteria: a study on planktonic and biofilm forms

“…Novel and unconventional methods for antimicrobial treatment are currently being explored for potential therapeutic applications. Some of the most promising approaches include bacteriophage therapy [12], repurposing existing drugs [13], antimicrobial peptides, small molecules, antibodies, natural compounds, anti-virulence agents, vaccines, immunomodulators, and employing silver nanoparticles (AgNPs) [14][15][16][17][18]. Amongst all the strategies stated previously, nanotechnology has shown good progress, and its influence has grown immensely in many sectors.…”

“…aerogenes [16,[33][34][35][36][37]. Although the precise mechanism remains unclear, studies suggest that AgNPs impact the bacterial cell membrane and interfere with ribosome and protein synthesis.…”