Based on two-hybrid analysis, CadC forms stable dimers in a stimulus- and linker-dependent manner, interacting only at pH 6.8; in addition, lysine is required for transducing the pH-dependent response of the periplasmic sensor into a structural rearrangement that facilitates dimerization of the cytoplasmic CadC DNA-binding domain [6]. The localization of CadC molecules in DNA, visible as clusters, is a result of a diffusion/capture mechanism dependent on the DNA [1].The mean search time of CadC to its DNA binding site was measured to be on average 4.5 min, regardless of the position on the chromosome of that site [7]. This search time decreased by a factor of two when a second site was introduced in the chromosome, which is consistent with the 2D diffusion and capture mechanism [7]. Based on mutational analysis, amino acids in the CadC DNA-binding domain (DBD) that are important for DNA recognition and function were identified. CadC utilizes non-sequence-specific and only a few specific interactions for complex formation [5] In the absence of lysine, LysP regulates CadC negatively [1, 4]. This inhibition is through intramembrane and periplasmic contacts under noninducing conditions. Based on site-directed mutagenesis, Asp275 and Asp278 in LysP and Arg265 and Arg268 in CadC were identified as residues for the stimulus-dependent interaction between them [8]. LysP and CadC interact most strongly at pH7.6 and at lysine concentrations of 1 µM or less, that is, under non-Cad-inducing conditions. This interaction is attenuated under Cad-inducing conditions (low pH, increased lysine levels). The LysP-CadC interaction is mediated via trans-membrane and periplasmic contacts [8]. Oligomerization of LysP is induced at low pH [8]. LysP is a trigger transporter [9], i.e., a protein that combines regulation and transport functions within the one polypeptide. At neutral cytoplasmic pH, a disulfide bond is formed in the periplasmic domain of CadC to inactivate it. At low pH, formation of the disulfide bond is prevented, which in turn converts CadC into an active state, but only if lysine is present to inactivate to LysP, the negative regulator of CadC [10]. Phylogenetic analysis revealed a higher complexity and more regulatory elements for the Cad system in E. coli than for that in Vibrio campbellii [11] The crystal structure of the CadC DNA-binding domain (DBD) has been determined [5] CadC appears to have a modest role in bacterial triclosan resistance [12].