Detection of mobile genetic elements conferring resistance to heavy metals in Salmonella 4,[5],12:i:- and Salmonella Typhimurium serovars and their association with antibiotic resistance

Salmonella enterica subsp. enterica serovar Typhimurium variant 4,[5],12:i:- (referred to as S. 4,[5],12:i:-) has emerged rapidly as the predominant Salmonella serovar in pigs, often associated with the acquisition of antibiotic resistance (ABR) and heavy metal resistance (HMR) genes. Our study analysed 78 strains of S. 4,[5],12:i:- (n = 57) and S. Typhimurium (n = 21), collected from 1999 to 2021, to investigate the evolution of mobile genetic elements (MGEs) containing HMR and ABR genes. Five MGEs harbouring HMR genes were identified: pUO-STVR2, pSTM45, pUO-STmRV1, SGI-4 and MREL. Among the strains, 91.23 % (52/57) of S. 4,[5],12:i:- carried at least one of these elements, compared to only 14.29 % (3/21) of S. Typhimurium. Since 2008, S. 4,[5],12:i:- have shifted from predominantly carrying pUO-STmRV1 to the emergence of SGI-4 and MREL, reducing ABR genes, reflecting the European Union ban on the use of antibiotics as feed additives. Increased resistance to copper and silver in S. 4,[5],12:i:-, conferred by SGI-4 and MREL, reflected that their acquisition was linked to the ongoing use of heavy metals in food-animal production. However, strains carrying SGI-4 and MREL still exhibit multidrug resistance, emphasising the need for targeted interventions to mitigate multidrug-resistant Salmonella spread in veterinary and public health settings.