Most cited article - PubMed ID 29203912
Bacterial resistance to silver nanoparticles and how to overcome it
Silver nanoparticles (AgNPs) are excellent antimicrobial agents and promising candidates for preventing or treating bacterial infections caused by antibiotic resistant strains. However, their increasing use in commercial products raises concerns about their environmental impact. In addition, traditional physicochemical approaches often involve harmful agents and excessive energy consumption, resulting in AgNPs with short-term colloidal stability and silver ion leaching. To address these issues, we designed stable hybrid lignin-silver nanoparticles (AgLigNPs) intended to effectively hit bacterial envelopes as a main antimicrobial target. The lignin nanoparticles (LigNPs), serving as a reducing and stabilizing agent for AgNPs, have a median size of 256 nm and a circularity of 0.985. These LigNPs were prepared using the dialysis solvent exchange method, producing spherical particles stable under alkaline conditions and featuring reducing groups oriented toward a wrinkled surface, facilitating AgNPs synthesis and attachment. Maximum accumulation of silver on the LigNP surface was observed at a mass reaction ratio mAg:mLig of 0.25, at pH 11. The AgLigNPs completely inhibited suspension growth and reduced biofilm development by 50% in three tested strains of Pseudomonas aeruginosa at a concentration of 80/9.5 (lignin/silver) mg L-1. Compared to unattached AgNPs, AgLigNPs required two to eight times lower silver concentrations to achieve complete inhibition. Additionally, our silver-containing nanosystems were effective against bacteria at safe concentrations in HEK-293 and HaCaT tissue cultures. Stability experiments revealed that the nanosystems tend to aggregate in media used for bacterial cell cultures but remain stable in media used for tissue cultures. In all tested media, the nanoparticles retained their integrity, and the presence of lignin facilitated the prevention of silver ions from leaching. Overall, our data demonstrate the suitability of AgLigNPs for further valorization in the biomedical sector.
- Publication type
- Journal Article MeSH
The outbreak of antibiotic-resistant bacteria, or "superbugs", poses a global public health hazard due to their resilience against the most effective last-line antibiotics. Identifying potent antibacterial agents capable of evading bacterial resistance mechanisms represents the ultimate defense strategy. This study shows that -the otherwise essential micronutrient- manganese turns into a broad-spectrum potent antibiotic when coordinated with a carboxylated nitrogen-doped graphene. This antibiotic material (termed NGA-Mn) not only inhibits the growth of a wide spectrum of multidrug-resistant bacteria but also heals wounds infected by bacteria in vivo and, most importantly, effectively evades bacterial resistance development. NGA-Mn exhibits up to 25-fold higher cytocompatibility to human cells than its minimum bacterial inhibitory concentration, demonstrating its potential as a next-generation antibacterial agent. Experimental findings suggest that NGA-Mn acts on the outer side of the bacterial cell membrane via a multimolecular collective binding, blocking vital functions in both Gram-positive and Gram-negative bacteria. The results underscore the potential of single-atom engineering toward potent antibiotics, offering simultaneously a long-sought solution for evading drug resistance development while being cytocompatible to human cells.
- Keywords
- antibiotic, cytocompatibility, manganese, multi‐drug resistance, single‐atom,
- MeSH
- Anti-Bacterial Agents * pharmacology chemistry MeSH
- Drug Resistance, Bacterial * drug effects MeSH
- Nitrogen chemistry MeSH
- Graphite chemistry pharmacology MeSH
- Humans MeSH
- Manganese chemistry MeSH
- Microbial Sensitivity Tests * MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- Nitrogen MeSH
- Graphite MeSH
- Manganese MeSH
Nanostructured materials with antibacterial activity face the same threat as conventional antibiotics - bacterial resistance, which reduces their effectiveness. However, unlike antibiotics, research into the emergence and mechanisms of bacterial resistance to antibacterial nanomaterials is still in its early stages. Here we show how Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria develop resistance to silver nanoparticles, resulting in an increase in the minimum inhibitory concentration from 1.69 mg/L for S. aureus and 3.38 mg/L for E. coli to 54 mg/L with repeated exposure over 12 and 6 cultivation steps, respectively. The mechanism of resistance is the same for both types of bacteria and involves the aggregation of silver nanoparticles leading to the formation of black precipitates. However, the way in which Gram-positive and Gram-negative bacteria induce aggregation of silver nanoparticles is completely different. Chemical analysis of the surface of the silver precipitates shows that aggregation is triggered by flagellin production in E. coli and by bacterial biofilm formation in S. aureus. However, resistance in both types of bacteria can be overcome by using pomegranate rind extract, which inhibits both flagellin and biofilm production, or by stabilizing the silver nanoparticles by covalently binding them to a composite material containing graphene sheets, which protects the silver nanoparticles from aggregation induced by the bacterial biofilm produced by S. aureus. This research improves the understanding of bacterial resistance mechanisms to nanostructured materials, which differ from resistance mechanisms to conventional antibiotics, and provides potential strategies to combat bacterial resistance and develop more effective antimicrobial treatments.
- MeSH
- Anti-Bacterial Agents * pharmacology chemistry MeSH
- Drug Resistance, Bacterial * drug effects MeSH
- Biofilms drug effects growth & development MeSH
- Escherichia coli * drug effects MeSH
- Metal Nanoparticles * chemistry MeSH
- Microbial Sensitivity Tests * MeSH
- Staphylococcus aureus * drug effects MeSH
- Silver * pharmacology chemistry MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- Silver * MeSH
A long-term exposure of bacteria to zinc oxide and zinc oxide nanoparticles leads to major alterations in bacterial morphology and physiology. These included biochemical and physiological processes promoting the emergence of strains with multi-drug resistance and virulence traits. After the removal of zinc pressure, bacterial phenotype reversed back to the original state; however, certain changes at the genomic, transcriptomic, and proteomic level remained. Why is this important? The extensive and intensive use of supplements in animal feed effects the intestinal microbiota of livestock and this may negatively impact the health of animals and people. Therefore, it is crucial to understand and monitor the impact of feed supplements on intestinal microorganisms in order to adequately assess and prevent potential health risks.
- Keywords
- antimicrobial resistance, genome, nanoparticles, phenotype, proteome, transcriptome, virulence, zinc, zinc oxide,
- MeSH
- Escherichia coli genetics MeSH
- Humans MeSH
- Multiomics MeSH
- Zinc Oxide * chemistry MeSH
- Proteomics MeSH
- Zinc * pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Zinc Oxide * MeSH
- Zinc * MeSH
It is generally recognized that the stability of nanoparticles (NPs) has a great impact on their potential biological applications. Despite this, very few studies have investigated the change in toxicity of NPs over time but none has studied the periodic physicochemical changes contributing to it. To address this, we analyzed the effects of long-term storage on the physicochemical changes of green synthesized silver nanoparticles (AgNPs) that directly influences their antimicrobial durability. Light-induced slow synthesis of AgNPs was carried out using Saraca asoca aqueous leaf extract. The synthesis was optimized with respect to parameters known to play a major role in the long-term stability of AgNPs: pH, temperature, light exposure time, AgNO3 concentration, extract proportion in the reaction mixture and storage conditions. Freshly synthesized AgNPs were characterized and then stored under optimized conditions. UV-vis spectrophotometry, AAS, conventional TEM and HR-TEM along with EDX spectroscopy were used at regular intervals to test the physicochemical properties that influence their long-term stability. Broth dilution assay was used to test antimicrobial activity of AgNPs against Escherichia coli and Staphylococcus aureus. Under dark storage conditions at room temperature, the AgNPs exhibited excellent stability with very good dispersity, throughout the study period of 18 months, despite the particles undergoing physicochemical changes in largescale. AgNPs exhibited sufficient antimicrobial activity against both strains tested. Due to the stronger stabilizing effect of the extract, we observed the lowest inhibition of E. coli and S. aureus by the freshly synthesized and 15 day old AgNPs; however, the inhibition rate escalated after a month and the highest rate of inhibition was observed with the particles between 2 months to 6 months of storage. After 6 months, we observed the particles losing their antimicrobial potential gradually, that lasted throughout the rest of our study period. This observation was in accord with the physicochemical changes that AgNPs were undergoing with time. By deepening our understanding of the changes in the physicochemical properties of green synthesized AgNPs over time, this study contributes to the development of more effective, durable, and potent AgNPs.
- Publication type
- Journal Article MeSH
The number of antibiotic-resistant bacterial strains is increasing due to the excessive and inappropriate use of antibiotics, which are therefore becoming ineffective. Here, we report an effective way of enhancing and restoring the antibacterial activity of inactive antibiotics by applying them together with a cyanographene/Ag nanohybrid, a nanomaterial that is applied for the first time for restoring the antibacterial activity of antibiotics. The cyanographene/Ag nanohybrid was synthesized by chemical reduction of a precursor material in which silver cations are coordinated on a cyanographene sheet. The antibacterial efficiency of the combined treatment was evaluated by determining fractional inhibitory concentrations (FIC) for antibiotics with different modes of action (gentamicin, ceftazidime, ciprofloxacin, and colistin) against the strains Escherichia coli, Pseudomonas aeruginosa, and Enterobacter kobei with different resistance mechanisms. Synergistic and partial synergistic effects against multiresistant strains were demonstrated for all of these antibiotics except ciprofloxacin, which exhibited an additive effect. The lowest average FICs equal to 0.29 and 0.39 were obtained for colistin against E. kobei and for gentamicin against E. coli, respectively. More importantly, we have experimentally confirmed for the first time, that interaction between the antibiotic's mode of action and the mechanism of bacterial resistance strongly influenced the combined treatment's efficacy.
- MeSH
- Anti-Bacterial Agents * chemistry pharmacology MeSH
- Ciprofloxacin pharmacology MeSH
- Escherichia coli MeSH
- Gentamicins pharmacology MeSH
- Colistin * pharmacology MeSH
- Microbial Sensitivity Tests MeSH
- Pseudomonas aeruginosa MeSH
- Drug Synergism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anti-Bacterial Agents * MeSH
- Ciprofloxacin MeSH
- Gentamicins MeSH
- Colistin * MeSH
The ability of bacteria to develop resistance to antibiotics is threatening one of the pillars of modern medicine. It was recently understood that bacteria can develop resistance even to silver nanoparticles by starting to produce flagellin, a protein which induces their aggregation and deactivation. This study shows that silver covalently bound to cyanographene (GCN/Ag) kills silver-nanoparticle-resistant bacteria at concentrations 30 times lower than silver nanoparticles, a challenge which has been so far unmet. Tested also against multidrug resistant strains, the antibacterial activity of GCN/Ag is systematically found as potent as that of free ionic silver or 10 nm colloidal silver nanoparticles. Owing to the strong and multiple dative bonds between the nitrile groups of cyanographene and silver, as theory and experiments confirm, there is marginal silver ion leaching, even after six months of storage, and thus very high cytocompatibility to human cells. Molecular dynamics simulations suggest strong interaction of GCN/Ag with the bacterial membrane, and as corroborated by experiments, the antibacterial activity does not rely on the release of silver nanoparticles or ions. Endowed with these properties, GCN/Ag shows that rigid supports selectively and densely functionalized with potent silver-binding ligands, such as cyanographene, may open new avenues against microbial resistance.
- Keywords
- antimicrobial, cytocompatibility, graphene, silver resistant,
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Bacterial Infections drug therapy MeSH
- Drug Resistance, Bacterial drug effects MeSH
- Metal Nanoparticles chemistry therapeutic use MeSH
- Silver chemistry therapeutic use MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Anti-Bacterial Agents MeSH
- Silver MeSH
Noble metals have played an integral part in human history for centuries; however, their integration with recent advances in nanotechnology and material sciences have provided new research opportunities in both academia and industry, which has resulted in a new array of advanced applications, including medical ones. Noble metal nanoparticles (NMNPs) have been of great importance in the field of biomedicine over the past few decades due to their importance in personalized healthcare and diagnostics. In particular, platinum, gold and silver nanoparticles have achieved the most dominant spot in the list, thanks to a very diverse range of industrial applications, including biomedical ones such as antimicrobial and antiviral agents, diagnostics, drug carriers and imaging probes. In particular, their superior resistance to extreme conditions of corrosion and oxidation is highly appreciated. Notably, in the past two decades there has been a tremendous advancement in the development of new strategies of more cost-effective and robust NMNP synthesis methods that provide materials with highly tunable physicochemical, optical and thermal properties, and biochemical functionalities. As a result, new advanced hybrid NMNPs with polymer, graphene, carbon nanotubes, quantum dots and core-shell systems have been developed with even more enhanced physicochemical characteristics that has led to exceptional diagnostic and therapeutic applications. In this review, we aim to summarize current advances in the synthesis of NMNPs (Au, Ag and Pt).
- Keywords
- Biomedical applications, Diagnostics, Noble metal nanoparticles, Personal healthcare, Therapeutics,
- Publication type
- Journal Article MeSH
- Review MeSH
AgNPs have attracted considerable attention in many applications including industrial use, and their antibacterial properties have been widely investigated. Due to the green synthesis process employed, the nanoparticle surface can be coated with molecules with biologically important characteristics. It has been reported that increased use of nanoparticles elevates the risk of their release into the environment. However, little is known about the behaviour of AgNPs in the eco-environment. In this study, the effect of green synthesized AgNPs on germinated plants of maize was examined. The effects on germination, basic growth and physiological parameters of the plants were monitored. Moreover, the effect of AgNPs was compared with that of Ag(I) ions in the form of AgNO3 solution. It was found that the growth inhibition of the above-ground parts of plants was about 40%, and AgNPs exhibited a significant effect on photosynthetic pigments. Significant differences in the following parameters were observed: weights of the caryopses and fresh weight (FW) of primary roots after 96 h of exposure to Ag(I) ions and AgNPs compared to the control and between Ag compounds. In addition, the coefficient of velocity of germination (CVG) between the control and the AgNPs varied and that between the Ag(I) ions and AgNPs was also different. Phytotoxicity was proved in the following sequence: control < AgNPs < Ag(I) ions.
- Keywords
- green synthesis, phyto-nanotechnology, phytotoxicity, plant physiology, thiol compounds,
- Publication type
- Journal Article MeSH
Biodegradable polymers are promising materials for use in medical applications such as stents. Their properties are comparable to commercially available resistant metal and polymeric stents, which have several major problems, such as stent migration and stent clogging due to microbial biofilm. Consequently, conventional stents have to be removed operatively from the patient's body, which presents a number of complications and can also endanger the patient's life. Biodegradable stents disintegrate into basic substances that decompose in the human body, and no surgery is required. This review focuses on the specific use of stents in the human body, the problems of microbial biofilm, and possibilities of preventing microbial growth by modifying polymers with antimicrobial agents.
- Keywords
- antimicrobial agents, antimicrobial effects, biodegradable polymer, medicine, polylactide, stent,
- Publication type
- Journal Article MeSH
- Review MeSH