Suggested functional model of Cus Regulon. The transmembrane efflux channel CusCBA consists of CusA, inner membrane protein; CusC, outer membrane protein and CusB, membrane fusion protein. CusF, a metallochaperone in periplasm, binds Ag+ and brings it to the efflux channel. The regulatory component of cus regulon CusRS which is a two-component regulatory system consists of CusS, sensor kinase and CusR, response regulator. The Cus regulon is activated in the presence of metal ions (Ag+, Cu++, Au+), for which CusS is auto-phosphorylated in the presence of metal ion (in this case Ag+) and trans-phosphorylates CusR, which binds with bidirectional cus promoter to activate RNA polymerase and transcription factor complex (adapted from Kim et al., 2011).