Abstract
There has been a recent surge in the use of silver as an antimicrobial agent in a wide range of domestic and clinical products, intended to prevent or treat bacterial infections and reduce bacterial colonization of surfaces. It has been reported that the antibacterial and cytotoxic properties of silver are affected by the assay conditions, particularly the type of growth media used in vitro. The toxicity of Ag+ to bacterial cells is comparable to that of human cells. We demonstrate that biologically relevant compounds such as glutathione, cysteine and human blood components significantly reduce the toxicity of silver ions to clinically relevant pathogenic bacteria and primary human dermal fibroblasts (skin cells). Bacteria are able to grow normally in the presence of silver nitrate at >20-fold the minimum inhibitory concentration (MIC) if Ag+ and thiols are added in a 1∶1 ratio because the reaction of Ag+ with extracellular thiols prevents silver ions from interacting with cells. Extracellular thiols and human serum also significantly reduce the antimicrobial activity of silver wound dressings Aquacel-Ag (Convatec) and Acticoat (Smith & Nephew) to Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli in vitro. These results have important implications for the deployment of silver as an antimicrobial agent in environments exposed to biological tissue or secretions. Significant amounts of money and effort have been directed at the development of silver-coated medical devices (e.g. dressings, catheters, implants). We believe our findings are essential for the effective design and testing of antimicrobial silver coatings.
Highlights
In recent years, the emergence and persistence of bacterial strains with resistance to multiple classes of antibiotics has led to renewed interest in the antimicrobial properties of silver
A key aim of this research is to ensure that silver ions are released at a sufficient rate and concentration to be effective as an antimicrobial at levels that are safe for use
Bacterial growth and microbiological assays Escherichia coli K12, P. aeruginosa PA01 [21], S. aureus MSSA476 and MRSA252 [22] were recovered from frozen (280uC) glycerol (15% v/v) stocks on Luria Bertani (LB) agar plates at 37uC for 24 hr
Summary
The emergence and persistence of bacterial strains with resistance to multiple classes of antibiotics has led to renewed interest in the antimicrobial properties of silver. A key aim of this research is to ensure that silver ions are released at a sufficient rate and concentration to be effective as an antimicrobial at levels that are safe for use This is important for the development of medical devices, such as wound dressings, catheters, bone implants and cardiovascular stents, which are typically tested first in vitro (antimicrobial assays and human cell culture) and later in vivo (animal models and clinical trials). Silver coatings on indwelling medical devices have been developed, such as the Bardex IC Foley catheter (Bard Medical) These coatings should release sufficient silver to reduce or prevent bacterial attachment and formation of biofilms whilst inducing minimal damage to surrounding human cells and tissue [8]. A recent study by Greulich et al used identical growth conditions for bacteria and human cells and this revealed that the antibacterial and cytotoxic properties of both silver ions (silver acetate) and silver nanoparticles are within the same range [10]
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