Abstract

BackgroundHeavy 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.ResultsWe 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.ConclusionOur 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.

Highlights

  • Heavy metal resistance (HMR) in Eubacteria is regulated by a variety of systems including transcription factors from the MerR family (COG0789)

  • Understanding the regulation of heavy metal resistance could be useful for biological waste treatment and estimating the impact that industrial activity may have on natural ecosystems

  • Bacterial metal resistance systems are regulated by transcriptional factors from the MerR family (COG0789), ArsR/SmtB family [50], two-component systems, such as CusRS, SilRS and PcoRS described in [2] and [3,4,46] respectively

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Summary

Introduction

Heavy metal resistance (HMR) in Eubacteria is regulated by a variety of systems including transcription factors from the MerR family (COG0789). 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. Understanding the regulation of heavy metal resistance could be useful for biological waste treatment and estimating the impact that industrial activity may have on natural ecosystems. Bacterial metal resistance systems are regulated by transcriptional factors from the MerR family (COG0789), ArsR/SmtB family [50], two-component systems, such as CusRS, SilRS and PcoRS described in [2] and [3,4,46] respectively. The structure of proteins from COG0789 has first been solved for BmrR and MtaN [16,17], followed by CueR and ZntR structures [18]

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