CuiD is a crucial gene for survival at high copper environment in Salmonella enterica serovar Typhimurium

Copper ion is an essential micronutrient but it is also extremely cytotoxic when it exists in excess. Our studies have shown that Salmonella enterica serovar Typhimurium can survive potentially lethal copper exposures by the way of copper efflux system. A copper ion inducible gene was identified in virulent S. typhimurium by using the technique of MudJ (Km, lac)-directed lacZYA operon fusions. A copper ion inducible strain LF153 (cuiD::MudJ) has been identified. The cuiD mutant exhibits a copper sensitive phenotype but possesses normal resistance to other metal ions, and lost DMP oxidase activity. Therefore, we suggest that cuiD is an important gene for copper homeostasis and the copper resistance response. The copper sensitive phenotype was complemented by pYL3.0 carrying cuiD+. Sequence analysis showed cuiD contains 1,614 bp encoding a 536 amino acid with a 27 amino acid signal peptide and a 509 amino acid residues comprising the mature peptide. The CuiD shows 81% homology to YacK, a putative multicopper oxidases which extrudes copper in Escherichia coli. This ORF contains four conserved regions that contain 12 copper ligands (types 1, 2, and 3) present in various copper homeostasis responsible proteins. The H2O2 sensitive phenotype of the cuiD mutant indicates that cuiD may be involved in oxidative stress response.