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Journal of Bacteriology, October 2000, p. 5864-5871, Vol. 182, No. 20
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Identification of a Copper-Responsive Two-Component
System on the Chromosome of Escherichia coli K-12
George P.
Munson,1,
Deborah L.
Lam,2
F. Wayne
Outten,1 and
Thomas V.
O'Halloran1,2,*
Department of Biochemistry, Molecular Biology, and
Cell Biology1 and Department of
Chemistry,2 Northwestern University,
Evanston, Illinois 60208-3113
Received 4 April 2000/Accepted 11 July 2000
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 pco
operon of E. coli; CopR and CopS from the
cop operon, which provides copper resistance to
Pseudomonas syringae; and SilR and SilS from the
sil locus, which provides silver ion resistance to
Salmonella enterica serovar Typhimurium. The genes
cusRS 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. The
cus 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 cusC
and additional downstream genes are homologous to known metal ion antiporters.
*
Corresponding author. Mailing address: Department of
Chemistry, Northwestern University, 2145 Sheridan Rd., Evanston, IL
60208-3113. Phone: (847) 491-5060. Fax: (847) 491-7713. E-mail:
t-ohalloran{at}nwu.edu.

Present address: Emory University, Atlanta,
GA.
Journal of Bacteriology, October 2000, p. 5864-5871, Vol. 182, No. 20
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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