Genetic regulation of the ramA locus and its expression in clinical isolates of Klebsiella pneumoniae.
Bottom Line: Like MarA, RamA binds the promoter region, implying that it might be subject to autoregulation.Intriguingly, levels of romA and ramA expression were not uniformly affected by changes within the ramR gene, thereby supporting the dual promoter finding.Furthermore, a subset of strains sustained no changes within the ramR gene but which still overexpressed the romA-ramA genes, strongly suggesting that a secondary regulator may control ramA expression.
Affiliation: Centre for Infection and Immunity, 4th Floor, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.Show MeSH
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Mentions: Expression of the ramA gene is controlled at a transcriptional level. Studies both in Salmonella enterica serovar Typhimurium  and K. pneumoniae have identified a tetR-like gene, called ramR, that lies upstream of the ramA gene and acts as its repressor (Fig. 1). Of note, the stop codon of the ramR gene overlaps the start codon of the ybdF gene, implying that regulation of these genes is very likely linked. Studies both into S. Typhimurium  and K. pneumoniae have reported that ramR mutations are directly linked to ramA overexpression. Both in Salmonella and Klebsiella, bioinformatic analyses suggest that the RamR protein binds a palindromic sequence that is either overlapping or downstream of the –10 sequence of the ramR gene [16,17]. In K. pneumoniae and Enterobacter spp., the genomic organisation of ramR, its corresponding palindromic binding sites and ramA is conserved compared with Salmonella, although these bacteria also harbour the romA gene (Fig. 1). Mutations within the ramR gene have been shown to result in ramA upregulation [16,17], however the effect of this derepression on the surrounding genes within the locus, i.e. romA, is not known.
Affiliation: Centre for Infection and Immunity, 4th Floor, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.