Antimicrobial activity of metals: mechanisms, molecular targets and applications

Lemire, Joseph; Harrison, Joe J.; Turner, Raymond J.

doi:10.1038/nrmicro3028

Cited by 2,212 publications

(1,715 citation statements)

References 164 publications

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“…In a study by Hardes et al [15], however, no local or systemic side-effects were reported after placement of Ag coated megaprostheses in 20 patients, although Ag blood levels exceeded 55 ppb, and 1600 ppb was detected in nearby tissue. As antibiotic resistance is spreading among pathogens, alternatives are sorely needed and a growing body of work is now dedicated to studying metal-based antimicrobials to treat infections [55].…”

Section: Discussionmentioning

confidence: 99%

Reactive combinatorial synthesis and characterization of a gradient Ag–Ti oxide thin film with antibacterial properties

et al. 2015

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Growing demand for orthopedic and dental implants has spurred researchers to develop multifunctional coatings, combining tissue integration with antibacterial features. A possible strategy to endow titanium (Ti) with antibacterial properties is by incorporating silver (Ag), but designing a structure with adequate Ag + release while maintaining biocompatibility has been shown difficult. To further explore the composition-structure-property relationships between Ag and Ti, and its effects against bacteria, this study utilized a combinatorial approach to manufacture and test a single sample containing a binary Ag-Ti oxide gradient. The sample, sputter deposited in a reactive (O 2 ) environment using a custom built combinatorial physical vapor deposition (PVD) system, was shown to be effective against Staphylococcus aureus with viability reductions ranging from 17 to above 99 %, depending on amount of Ag + released from its different parts. The Ag content along the gradient ranged from 35 to 62 wt%, but it was found that structural properties such as varied porosity and degree of crystallinity, rather than amount of incorporated Ag governed the Ag + release and resulting antibacterial activity. The coating also demonstrated in vitro apatite forming abilities, where structural variety along the sample was shown to alter the hydrophilic behavior, with degree of hydroxyapatite (HA) deposition varying accordingly. By means of combinatorial synthesis, a single gradient sample was able to display intricate compositional and structural features affecting its biological response, which would otherwise require a series of coatings. The current findings suggest that future implant coatings incorporating Ag as an antibacterial agent could be structurally enhanced to better suit clinical requirements.

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Section: Discussionmentioning

confidence: 99%

Reactive combinatorial synthesis and characterization of a gradient Ag–Ti oxide thin film with antibacterial properties

et al. 2015

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“…Several articles have also been written to explain mechanistically the mode of action of silver nanoparticles [15][16][17][18][19]. However, most work focused on the empirical observations of effects that lead to the eradication of the target microbes, and very little rationalization on the general antimicrobial pathways was performed.…”

Section: Introductionmentioning

confidence: 99%

“…Only general trends will thus be described. More information can be found in excellent reviews on the subject [15][16][17][18][19]. Additionally, toxicity issues for humans (systemic and at the cellular level) are topics of primary concern related to Ag NPs, but will not be developed here.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial activity of silver nanoparticles: A surface science insight

2015

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Summary Silver nanoparticles constitute a very promising approach for the development of new antimicrobial systems. Nanoparticulate objects can bring significant improvements in the antibacterial activity of this element, through specific effect such as an adsorption at bacterial surfaces. However, the mechanism of action is essentially driven by the oxidative dissolution of the nanoparticles, as indicated by recent direct observations. The role of Ag + release in the action mechanism was also indirectly observed in numerous studies, and explains the sensitivity of the antimicrobial activity to the presence of some chemical species, notably halides and sulfides which form insoluble salts with Ag + . As such, surface properties of Ag nanoparticles have a crucial impact on their potency, as they influence both physical (aggregation, affinity for bacterial membrane, etc.) and chemical (dissolution, passivation, etc.) phenomena. Here, we review the main parameters that will affect the surface state of Ag NPs and their influence on antimicrobial efficacy. We also provide an analysis of several works on Ag NPs activity, observed through the scope of an oxidative Ag + release.

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“…However, selection of in vitro models is often arbitrary, as well as the chosen nanoparticles and exposure conditions. Silver nanoparticles (AgNPs) are interesting for a mechanistic evaluation of in vitro tests because their mechanism of action is suggested to depend on both Ag + and NPs (Ivask et al, 2014;Lemire et al, 2013). In suspension, AgNPs have been described to release ions (Kittler et al, 2010), which strongly contribute to the biological activity of AgNPs in vitro and in vivo (Bouwmeester et al, 2011;Foldbjerg et al, 2012;van der Zande et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

et al. 2016

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The mode of action of silver nanoparticles (AgNPs) is suggested to be exerted through both Ag + and AgNP dependent mechanisms. Ingestion is one of the major NP exposure routes, and potential effects are often studied using Caco-2 cells, a well-established model for the gut epithelium. MCF-7 cells are epithelial breast cancer cells with extensive well-characterized toxicogenomics profiles. In the present study, we aimed to gain a deeper understanding of the cellular molecular responses in Caco-2 and MCF-7 cells after AgNP exposure in order to evaluate whether epithelial cells derived from different tissues demonstrated similar responses. These insights could possibly reduce the size of cell panels for NP hazard identification screening purposes. AgNPs of 20, 30, 60, and 110 nm, and AgNO 3 were exposed for 6 h and 24 h. AgNPs were shown to be taken up and dissolve intracellularly. Compared with MCF-7 cells, Caco-2 cells showed a higher sensitivity to AgNPs, slower gene expression kinetics and absence of NP size-dependent responses. However, on a molecular level, no significant differences were observed between the two cell types. Transcriptomic analysis showed that Ag(NP) exposure caused (oxidative) stress responses, possibly leading to cell death in both cell lines. There was no indication for effects specifically induced by AgNPs. Responses to AgNPs appeared to be induced by silver ions released from the AgNPs. In conclusion, differences in mRNA responses to AgNPs between Caco-2 and MCF-7 cells were mainly related to timing and magnitude, but not to a different underlying mechanism.

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Antimicrobial activity of metals: mechanisms, molecular targets and applications

Cited by 2,212 publications

References 164 publications

Reactive combinatorial synthesis and characterization of a gradient Ag–Ti oxide thin film with antibacterial properties

Reactive combinatorial synthesis and characterization of a gradient Ag–Ti oxide thin film with antibacterial properties

Antibacterial activity of silver nanoparticles: A surface science insight

Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action

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