Since time immemorial, silver has been used in medicine as an antimicrobial agent . Even today, silver is used in hospitals as an antiseptic on burned skin and in implanted catheters. It is not considered an essential trace metal because of its toxicity. In nature, silver-resistant bacteria have been evolved [92-101]. Although reduced accumulation of silver by silver-resistant bacteria was observed, binding of silver to other intracellular compounds like H2S and phosphate also always occurred .
The copper-effluxing ATPase CopB from E. hirae was found to transport Ag as well as Cu ; the Km for both substrates was identical. Genome analysis of Pseudomonas putida revealed that SilP and PacS are the prospective proteins involved in the transport of monovalent cations (Cu and/or Ag). The corresponding genomic segment is located in a large gene cluster probably involved in Ag resistance and/or Cu homoeostasis . The Ag/Cu-related genomic segment could encode a P-type ATPase (putative SilP), a three polypeptide cation/proton antiporter (putative CusCBA), as well as metal-binding proteins (CopAB1); this could all be regulated by a two-component regulatory system (putative CopSR1)  resembling the sil gene of Salmonella plasmid pMG101 isolated from a hospital burn ward . Summarily, silver resistance may be based on RND-driven transenvelope efflux in Gram-negative bacteria; efflux by P-type ATPases in Gram-positive organisms; and additional complexation by intracellular compounds.
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