Effect of Silver Content on the Structure and Antibacterial Activity of Silver-Doped Phosphate-Based Glasses

Abstract

Staphylococcus aureus can cause a range of diseases, such as osteomyelitis, as well as colonize implanted medical devices. In most instances the organism forms biofilms that not only are resistant to the body's defense mechanisms but also display decreased susceptibilities to antibiotics. In the present study, we have examined the effect of increasing silver contents in phosphate-based glasses to prevent the formation of S. aureus biofilms. Silver was found to be an effective bactericidal agent against S. aureus biofilms, and the rate of silver ion release (0.42 to 1.22 g ⅐ mm ؊2 ⅐ h ؊1 ) from phosphate-based glass was found to account for the variation in its bactericidal effect. Analysis of biofilms by confocal microscopy indicated that they consisted of an upper layer of viable bacteria together with a layer (ϳ20 m) of nonviable cells on the glass surface. Our results showed that regardless of the silver contents in these glasses (10, 15, or 20 mol%) the silver exists in its ؉1 oxidation state, which is known to be a highly effective bactericidal agent compared to that of silver in other oxidation states (؉2 or ؉3). Analysis of the glasses by 31 P nuclear magnetic resonance imaging and high-energy X-ray diffraction showed that it is the structural rearrangement of the phosphate network that is responsible for the variation in silver ion release and the associated bactericidal effectiveness. Thus, an understanding of the glass structure is important in interpreting the in vitro data and also has important clinical implications for the potential use of the phosphate-based glasses in orthopedic applications to deliver silver ions to combat S. aureus biofilm infections.Staphylococcus aureus, a leading cause of nosocomial infections worldwide, is the etiological agent of a wide range of diseases, from relatively benign skin infections to potentially fatal systemic disorders (41). Many of these diseases, including endocarditis, osteomyelitis, and foreign body-related infections, appear to be caused by biofilm-associated S. aureus (14,18,27,38). Biofilms are sessile communities characterized by cells that are attached to a substratum or interface or to each other, embedded in a matrix of extracellular polymeric substances that they have produced, and exhibit an altered phenotype with respect to growth rate and gene transcription (14). Biofilm formation occurs as a result of a sequence of events: microbial surface attachment, cell proliferation, matrix production, and detachment (34). Biofilm-associated bacteria show decreased susceptibilities to antibiotics (10), disinfectants (31), and clearance by host defenses (14, 37). Work by Mulligan et al. (29,30) showed that the inclusion of copper or silver ions in phosphate-based glasses was useful in treating biofilms of Streptococcus sanguis. Silver cations exhibit broad antimicrobial action at low concentrations, and they are already being used for the treatment of burn wounds (32) and traumatic injuries (5, 15). Feng et al. (15) studied the antibacterial effects of si...

An Excursion into the Intriguing World of Polymeric Tl(I) and Ag(I) Cyanoximates

“…It is reported that the incorporation of silver into implants is a most promising method in reducing the infection rate, while exhibiting low toxicity towards cells and tissues [60]. Silver incorporating biomaterials, therefore, have tremendous potential for advancing the safety of internal implant therapies in the health care industry [61][62][63]. With the exception of several publications [64][65][66][67], there were no systematic studies regarding light-, heat-, chemically stable, water insoluble silver(I) antimicrobial compounds targeting specific infections, and no oxime-based compounds were tested on that matter at all.…”

Silver-coated carbon nanotubes downregulate the expression of Pseudomonas aeruginosa virulence genes: a potential mechanism for their antimicrobial effect

“…2,3 Although the antimicrobial activity of silver is well known, its mechanism of action is not yet fully understood. Several mechanisms have been proposed, such as a loss of the replication ability of DNA 4 and changes in membrane structure. 5 Carbon nanotubes (CNTs) are used in many nanocomposites, because they possess distinct mechanical and electronic properties.…”

Effect of Silver-Doped Phosphate-Based Glasses on Bacterial Biofilm Growth

“…Biofilm-associated bacteria show decreased susceptibilities to antibiotics (4), disinfectants (13), and clearance by host defenses (7,16). Hence, the development of alternative strategies for combating biofilm-associated infections, such as the use of controlled metal ion-releasing phosphate-based glasses (PBGs), is of considerable interest (10,19). Silver cations exhibit broad antimicrobial activity at low concentrations, and they are already being used for the treatment of burn wounds (14) and traumatic injuries (3).…”

“…Ahmed et al (1,2) have shown that PBGs containing silver in its ϩ1 oxidation state exert antibacterial effects against planktonic P. aeruginosa and S. aureus. Valappil et al (19) reported that 10, 15, and 20 mol% levels of silver in PBGs were useful in preventing the growth of S. aureus biofilms. However, striking a balance between antimicrobial and cyto-/biocompatibility is of major importance for the in vivo clinical application of these PBGs.…”