The thioredoxin system,
which is composed of NADPH, thioredoxin reductase (TrxR), and thioredoxin
(Trx), is one of the major disulfide reductase systems used by bacteria
against oxidative stress. In particular, this reductase system is
crucial for the survival of the pathogenic bacterium <i>Staphylococcus
aureus</i>, which lacks a natural glutathione/glutaredoxin (Grx)
system. Although silver ions and silver-containing materials have
been used as antibacterial agents for centuries, the antibacterial
mechanism of silver is not well-understood. Herein, we demonstrate
that silver ions bind to the active sites of <i>S. aureus</i> TrxR and Trx with dissociation constants of 1.4 ± 0.1 μM
and 15.0 ± 5.0 μM and stoichiometries of 1 and 2 Ag<sup>+</sup> ions per protein, respectively. Importantly, silver ion binding
leads to oligomerization and functional disruption of TrxR as well
as Trx. Silver also depleted intracellular thiol levels in <i>S. aureus</i>, disrupting bacterial thiol-redox homeostasis.
Our study provides new insights into the antibacterial mechanism of
silver ions. Moreover, the Trx and TrxR system might serve as a feasible
target for the design of antibacterial drugs
