Analysis of 56K genomes identifies the relationship between antibiotic and metal resistance co-Occurrence and the spread of multidrug-resistant non-typhoidal Salmonella

Salmonella enterica is common foodborne pathogen that generates both enteric and systemic infections in hosts. Antibiotic resistance is common is certain serovars of the pathogen and of great concern to public health. Recent reports have documented the co-occurrence of metal resistance with antibiotic resistance in one serovar of S. enterica. Therefore, we sought to identify possible co-occurrence in a large genomic dataset. Genome assemblies of 56,348 strains of S. enterica comprising 20 major serovars were downloaded from NCBI. The downloaded assemblies were quality controlled and in silico serotyped to ensure consistency and avoid improper annotation from public databases. Metal and antibiotic resistance genes were identified in the genomes as well as plasmid replicons. Co-current genes were identified by constructing a co-occurrence matrix and group the genes using k-means clustering. Three groups of co-occurrent genes were identified using k-means clustering. Group 1 was comprised of the pco and sil operons that confer resistance to copper and silver respectively. Group 1 was distributed across four serovars. Group 2 contained the majority of the genes and little to no co-occurrence was observed. Metal and antibiotic co-occurrence was identified in group 3 that contained genes conferring resistance to: arsenic, mercury, beta-lactams, sulfonamides, and tetracyclines. Group 3 genes were also associated with an IncQ1 class plasmid replicon. Metal and antibiotic co-occurrence was isolated to one clade of S. enterica I 4,[5],12:i:.