Research article

Comparative genomics of regulation of heavy metal resistance in Eubacteria

EA Permina^{* 1} , AE Kazakov^{* 2} , OV Kalinina³ and MS Gelfand²

¹State Research Institute of Genetics and Selection of Industrial Microorganisms, 1st Dorozhnyj proezd, 1, Moscow, 113535, Russia

²Institute for Information Transmission Problems, Russian Academy of Science, Bolshoi Karetny per. 19, Moscow 127994, Russia

³Department of Bioengineering and Bioinformatics, Moscow State University, Laboratory Building B, Vorobiovy Gory 1-73, Moscow 119992, Russia

author email corresponding author email* Contributed equally

BMC Microbiology 2006, 6:49doi:10.1186/1471-2180-6-49

Published:	5 June 2006

Abstract

Background

Heavy metal resistance (HMR) in Eubacteria is regulated by a variety of systems including transcription factors from the MerR family (COG0789). The HMR systems are characterized by the complex signal structure (strong palindrome within a 19 or 20 bp promoter spacer), and usually consist of transporter and regulator genes. Some HMR regulons also include detoxification systems. The number of sequenced bacterial genomes is constantly increasing and even though HMR resistance regulons of the COG0789 type usually consist of few genes per genome, the computational analysis may contribute to the understanding of the cellular systems of metal detoxification.

Results

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.

Conclusion

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.