The pervasive environmental metal contamination has led to selection of heavy-metal resistance genes in bacteria. The and clusters are located on a mobile genetic element and linked to heavy-metal resistance. These clusters have been found in serovars isolated from human clinical cases and foods of animal origin. This may be due to the use of heavy metals, such as copper, in animal feed for their antimicrobial and growth promotion properties. The cluster can be found alone or in combination with cluster, either in the chromosome or on a plasmid. Previous reports have indicated that , but not cluster contributes to copper resistance in Typhimurium. However, the role of the cluster on the physiology of non-typhoidal remains poorly understood. To understand the function of the gene cluster, a deletion mutant of genes was constructed using allelic exchange mutagenesis. Deletion of genes inhibited growth of in high-copper medium, but only under anaerobic environment. Complementation of the mutant reversed the growth phenotype. The survival of in RAW264.7 macrophages was not affected by the loss of genes. This study indicates that the acquired cluster is crucial for copper detoxification in , but it is not essential for intracellular replication within macrophages.