Despite the long history of silver as an antimicrobial, the mechanism of this activity remains a matter of active research.
The general explanation offered is that silver kills by at least one of the following mechanisms:
(a) interference with vital cellular processes by binding to sulfhydryl or disulfide functional groups on the surfaces of membrane proteins and other enzymes;
(b) disruption of DNA replication; and
(c) oxidative stress through the catalysis of reactive oxygen species (ROS) formation. However, controversy exists regarding which of these mechanisms is most important.
For instance, one study presented evidence which showed that silver binding specifically to membrane proteins disrupts ion and proton transport across the membrane, while another found that Ag ions permeate to the cellular interior, where they interfere with ribosomal activity and disrupt the production of several key enzymes responsible for energy production.
With respect to interference of DNA replication, cell wall damage resulting from silver binding to membrane proteins and DNA condensation in Escherichia coli and Staphylococcus aureus has been observed; the condensation of DNA in response to the presence of Ag ions has been cited as a defense mechanism, which, while protecting the DNA from harm, limits the ability of cells to self-replicate.
In contrast, a separate report asserted that Ag complexes of glutamic and tartaric acids actively interfere with DNA unwinding, and suggested that Ag ion binding to enzymes and membrane proteins is a comparatively minor contributor to silver’s antimicrobial effect.
Gram-negative bacteria (e.g., E. coli) are generally more susceptible to silver treatment than Gram-positive bacteria (e.g., S. aureus) because transport of positively charged silver ions across the thicker, peptidoglycan-rich outer membranes of Gram-positive bacteria is slow relative to transport across the thinner membranes of Gram-negative specimens.
Finally, there is evidence that the antibacterial activity of silver zeolites derives from silver’s ability to catalyze the production of reactive oxygen species, which causes cell death by creating oxidative stress ; in support of this idea, antioxidant rich Bacillus spores are highly resistant to silver antimicrobials, whereas vegetative and relatively anti-oxidant poor Bacillus cells are quite vulnerable.
It is certainly possible that all of these mechanisms contribute to the antimicrobial activity of silver, which would explain its broad effectiveness as well as the infrequent reports of silver-resistant bacterial strains.