# Silver Nanowires: Synthesis, Antibacterialativity and Biomedical Applications
## 3 Mechanism of Antibacterial Activity  
### Silver Nanoparticles Mechanism of Action  
Silver is currently present in a vast number of consumer products in the form of engineered materials and nanomaterials. Antimicrobial activity has been demonstrated for many different materials containing silver, but it has become evident that the mechanism of action of bulk silver may substantially differ from that of nanosilver [52], although the mechanism by which silver nanospecies elicit their antibacterial effects remains elusive. Three hypothesized mechanisms of action for silver nanomaterials have been reported in some depth in a review by [PERSON] and [PERSON] [52]. These three main mechanisms of antibacterial action, detailed below, are consistently hypothesized for AgNPs and are reported as directly causing or contributing also to the antibacterial activity of AgNPs.  
The first commonly reported mechanism of antibacterial action is based on the generation of silver ions by oxidation of the metallic silver that forms AgNPs. The oxidation reaction has been speculated to be dependent on either a reaction with hydrogen peroxide in acidic medium in the bacterial cell membrane [53] or by reaction with oxygen [54]. Once released, the ions are free to interact with the bacterial cell membrane resulting in direct cell damage [19; 55]. Furthermore, silver ions have been reported to have high affinity for the thiol groups of cysteine residues, and therefore favor interaction with respiration chain proteins [56]; this allows the ions to strongly bind to transport pumps leading to proton leakage and a decrease in proton motive force [57]. Silver ions can also inhibit uptake of phosphate resulting in efflux of extracellular phosphate [57; 58] and cause extreme cytoplasmic shrinkage and detachment of the cell membrane, resulting in cell wall degradation and eventual leakage of intracellular contents [40; 44].  
A second proposed mechanism is centered upon the formation of reactive oxygen species (ROS) and their effect on bacterial cells [59; 60; 61]. It has been theorized that silver ions enhance the generation of ROS by interacting with the thiol groups on the respiratory chain enzymes [62] or by directly interacting and inhibiting the action of free radical scavenging enzymes, such as superoxide dismutase [63; 64]. This results in an increased presence of ROS, which attack membrane lipids and DNA, resulting in faulty replication [65; 66].  
The final commonly suggested mechanism is direct physical damage by silver nanospecies and silver ions adhering to the surface of bacterial cells [53]. Various reports have suggested different mechanisms for adherence of silver to bacterial membranes. One potential mechanism is that the negatively charged bacterial surface attracts the positively charged Ag\({}^{+}\). However, metallic silver nanocrystals are thought to possess a negative charge, in this case as the bacterial cell and the crystal become closer the repulsive forces are overcome and strong attractive forces are present [67]. It is important to note that this mechanism has been recently disputed by [PERSON] et al. [68], who discovered unusual protein damage on _E. coli_ cells, which has led to the suggestion that silver nanospecies bind to sulfur-containing proteins within the cell membrane and result in direct membrane damage [69; 70].