Comparative approach to analysis of regulation in complete genomes: multidrug resistance systems in gamma-proteobacteria.

Comparative approach is a powerful tool for analysis of gene regulation in bacterial genomes. Here we apply it to analysis of regulation of the multidrug resistance transport (MDRT) systems in enterobacteria Escherichia coli, Salmonella typhi, Klebsiella pneumoniae and Yersinia pestis. Comparison of nucleotide sequences upstream of MDRT genes was performed in order to predict new regulatory sites (operators) and identify candidate regulons. Since the regulatory sites diverge slower than the non-coding regions in general, they are visible as strongly conserved islands. This analysis resulted in description of a regulatory network for known and hypothetical MDRT systems and porins. New candidate members of the MarA regulon were detected. Putative binding sites for EmrR and AcrR were suggested. A new hypothetical MarX regulon was described that includes some multidrug transporters and porins.