Molecular characterization of the copper transport system in Staphylococcus aureus.

The Staphylococcus aureus copA gene codes for a putative copper-translocating P-type ATPase and the downstream copZ gene codes for a copper chaperone. Genome database analyses demonstrate that these copper transport genes are highly conserved in S. aureus. The expression of copA and copZ was inducible by copper and to some extent by ferric and lead ions. A mutant strain containing a partially deleted copA gene was more sensitive than the parent strain to copper, ferric and lead ions. The copper-sensitive phenotype was due to the accumulation of intracellular copper and thus the copA product is involved in the export of copper ions. The metal-sensitive phenotype of the mutant was complemented in trans by a 2.7 kbp DNA containing copA. We have cloned and overexpressed the metal-binding domains of CopA and CopZ and have shown by site-directed mutagenesis that the cysteine residues in the CXXC metal-binding motif in CopA are involved in copper binding and thus play an important role in copper transport in S. aureus.