Identification of a Copper-Responsive Two-Component System on the Chromosome of Escherichia coli K-12

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Abstract
Using a genetic screen we have identified two chromosomal genes,cusRS (ylcA ybcZ), from Escherichia coli K-12 that encode a two-component, signal transduction system that is responsive to copper ions. This regulatory system is required for copper-induced expression of pcoE, a plasmid-borne gene from the E. coli copper resistance operon pco. The closest homologs of CusR and CusS are plasmid-borne two-component systems that are also involved in metal responsive gene regulation: PcoR and PcoS from the pcooperon of E. coli; CopR and CopS from thecop operon, which provides copper resistance toPseudomonas syringae; and SilR and SilS from thesil locus, which provides silver ion resistance toSalmonella enterica serovar Typhimurium. The genescusRS are also required for the copper-dependent expression of at least one chromosomal gene, designated cusC(ylcB), which is allelic to the recently identified virulence gene ibeB in E. coli K1. Thecus locus may comprise a copper ion efflux system, because the expression of cusC is induced by high concentrations of copper ions. Furthermore, the translation products of cusCand additional downstream genes are homologous to known metal ion antiporters.