Comparative genomics of regulation of heavy metal resistance in Eubacteria

We studied the mercury (MerR), copper (CueR and HmrR), cadmium (CadR), lead (PbrR), and zinc (ZntR) resistance systems and demonstrated that combining protein sequence analysis and analysis of DNA regulatory signals it was possible to distinguish metal-dependent members of COG0789, assign specificity towards particular metals to uncharacterized loci, and find new genes involved in the metal resistance, in particular, multicopper oxidase and copper chaperones, candidate cytochromes from the copper regulon, new cadmium transporters and, possibly, glutathione-S-transferases.Our data indicate that the specificity of the COG0789 systems can be determined combining phylogenetic analysis and identification of DNA regulatory sites. Taking into account signal structure, we can adequately identify genes that are activated using the DNA bending-unbending mechanism. In the case of regulon members that do not reside in single loci, analysis of potential regulatory sites could be crucial for the correct annotation and prediction of the specificity.Some metals, including iron, zinc, copper, manganese, etc. are micronutrients used in the redox processes, regulation of the osmotic pressure, and also enzyme components. Other metals are not essential. However, even essential metals such as zinc and copper are toxic at high concentrations. The effects of high metal concentration are DNA and membrane damage and loss of enzyme function. To protect themselves from toxic metals concentrations, bacteria utilize a variety of resistance mechanisms that involve permeability barriers, intra- and extracellular sequestration, efflux pumps, enzymatic detoxification and reduction [1].Though heavy metals are naturally present in some ecosystems, their industrial use leads to serious environmental problems. The use of metal-resistance bacteria can help to remove metal from contaminated environments. Understanding the regulation of heavy metal resistance could be useful for biological waste treatment