Silver nanoparticles: Antimicrobial activity, cytotoxicity, and synergism with N‐acetyl cysteine

Abstract

The fast progression of nanotechnology has led to novel therapeutic interventions. Antimicrobial activities of silver nanoparticles (Ag NPs) were tested against standard ATCC strains of Staphylococcus aureus (ATCC 9144), Escherichia coli (O157:H7), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 90028) in addition to 60 clinical isolates collected from cancer patients. Antimicrobial activity was tested by disk diffusion method and MIC values for Ag NPs alone and in combination with N-acetylcysteine (NAC) against tested pathogens were determined by broth microdilution method. Ag NPs showed a robust antimicrobial activity against all tested pathogens and NAC substantially enhanced the antimicrobial activity of Ag NPs against all tested pathogens. Synergism between Ag NPs and NAC has been confirmed by checkerboard assay. The effect of Ag NPs on tested pathogens was further scrutinized by Transmission Electron Microscope (TEM) which showed disruption of cell wall in both bacteria and fungi. Ag NPs abrogated the activity of respiratory chain dehydrogenase of all tested pathogens and released muramic acid content from S. aureus in culture. The cytotoxic effect of Ag NPs alone and in combination with NAC was examined using human HepG2 cells and this revealed no cytotoxicity at MIC values of Ag NPs and interestingly, NAC reduced the cytotoxic effect of Ag NPs at concentrations higher than their MIC values. Taken together, Ag NPs have robust antimicrobial activity and NAC substantially enhances their antimicrobial activities against MDR pathogens which would provide a novel safe, effective, and inexpensive therapeutic approach to control the prevalence of MDR pathogens.

<p>Antibacterial activity and mechanism of silver nanoparticles against multidrug-resistant <em>Pseudomonas aeruginosa</em></p>

“…26 Previous studies proved that AgNPs could interrupt the respiratory chain reaction in bacteria by combining the sulfhydryl units of dehydrogenase and inhibiting its activity. 16 We speculate that AgNPs may curb dehydrogenase activity in P. aeruginosa and disturb the reaction of aerobic respiration and oxidative phosphorylation, resulting in accumulation of ROS and initiation of oxidative stress response in the bacteria. Actually, based on TMT-labeled quantitative proteomic analysis, our results implied that, after AgNP treatment, the oxidative stress reaction in the bacteria was strengthened with obvious high expression of SOD, CAT, and POD (such as AhpD, AhpC, AhpF, and Ohr).…”

“…14 Moreover, the antimicrobial mechanisms of AgNPs on multidrug-resistant bacteria remain enigmatic. Currently, the most known mechanisms of AgNPs involve 1) AgNPs disrupt the integrity of the bacterial cell wall and membrane, promoting the permeability of the membrane and the leakage of the cell constituents, and eventually induce cell death; 15 2) AgNPs interrupt the respiratory chain reaction by combining the sulfhydryl, resulting in lipid peroxidation and oxidative damage of DNA and proteins, and then the cell death; 16,17 3) AgNPs bind to sulfur and phosphorous groups of the DNA, which leads to damage and aggregation of the DNA and disrupt its transcription and translation; 18 4) AgNPs foster dephosphorylation of phosphotyrosines, and thereby interfere the process of cell signal transduction and killing the cells; 15 5) when AgNPs are exposed to aerobic conditions, they could release Ag + from the surface of the particles. The released Ag + plays strong antimicrobial roles by interacting with the cell membrane and cell wall components of the bacteria, which is one of the crucial mechanisms of toxicity of AgNPs.…”

Design of Immobilized Enzyme Biocatalysts: Drawbacks and Opportunities

“…150,151 Many studies are designed to minimize the release of silver into the environment, since this metal is widely used in several products because it has antimicrobial potential. 152,[161][162][163] A study was carried out to investigate the controlled release of immobilized silver nanoparticles in thin layer of aluminum oxide. A 15 nm layer of this oxide is capable of inhibiting the release of silver for up to 48 h, since a 2 nm layer delayed the release for 4 h. 164 Another release study using nanoparticles was the work done by Mohammady et al, 165 obtaining nanoparticles with a mean size of 120 to 300 nm from the poly-lactide-co-glycolide polymer (PLGA).…”

Detection of blaSPM-1 and blaSIM-2 Metallo-β-Lactamases Genes in Imipenem-Resistant Pseudomonas aeruginosa Clinical Isolates Recovered from Two University Hospitals in Egypt

“…Infections caused by this pathogen are often difficult to be treated because of both its intrinsic resistance and its remarkable ability to acquire further resistance mechanisms to a plethora of antibiotics 4,5 . Despite improvements in antibiotic therapy, there is still an escalating difficulty in finding new antibiotics and search for alternative approaches to combat drug resistance 1,6 .…”