ICEmST contributes to colonization of Salmonella in the intestine of piglets

Salmonella enterica serovar 4,[5],12:i:- sequence type 34 (ST34) has recently become a global concern for public and animal health. The acquisition of mobile genetic element ICEmST, which contains two copper tolerance gene clusters, cus and pco , influences the epidemic success of this clone. Copper is used as a feed additive in swine at levels that potentially lead to selection pressure for Enterobacteriaceae ; however, it remains unclear whether the copper tolerance system of ICEmST functions in vivo. We performed competition assays with Salmonella 4,[5],12:i:- ST34 wildtype (WT) and deletion mutants of ICEmST (ΔICEmST, Δ cus , and Δ pco ) in groups of mice fed 0, 150, and 500 ppm CuSO 4 . In the competition of WT against ΔICEmST and Δ cus , the competitive index of the 500 ppm-fed group was significantly lower than that of the 0 ppm-fed group. In the swine experiment, all individuals were fed 150 ppm CuSO 4 . The number of ICEmST-positive strain in the feces was significantly greater than that of ICEmST-negative strain. The serum inflammatory markers were significantly increased in swine infected with the ICEmST-positive strain. These data suggest that ICEmST, especially cus , provides Salmonella with the ability to colonize in the intestine, even at high copper concentrations, leading to swine salmonellosis.