Global population structure and genomic surveillance framework of carbapenem-resistant Salmonella enterica

Due to the frequent international and intercontinental transmission of multidrug-resistant bacteria, it is imper-ative to understand the epidemiology, phylogeography, and population structure of carbapenem-resistant Sal-monella enterica (CRSE) across the globe. During the period of 2015-2022, two blaNDM-carrying S. enterica strains were recovered from 3695 Salmonella strains in four hospitals in China. The global phylogenetic framework and geographical distribution of CRSE were defined by our recently updated bacterial whole genome sequence typing and source tracking database BacWGSTdb 2.0 to measure the diversity and evolutionary relatedness in context with epidemiological metadata. Phylogeny for all carbapenemase gene-harboring plasmids in S. enterica based on the pairwise Mash differences was also constructed to evaluate the potential transmission of these plasmids in a global context. A large-scale phylogenetic analysis grouped global CRSE into nine distinct clades. The small genetic distance (< 20 SNPs) between 198 pairs of CRSE suggested the presence of clonal transmission. Global CRSE have significant geographical variations, which was associated with the clonal lineages and carbapenemase genes. Carbapenemase gene-carrying plasmids with a high degree of similarity have surfaced in various hosts and countries. The widespread of multiple-replicon plasmids that offer a great capacity to accommodate multiple antimicrobial resistance genes is continuously enhancing the potential risk of CRSE isolates to propagate glob-ally. Both clonal spread of strains and horizontal transfer of carbapenemase gene-harboring plasmids contribute to the global dissemination of CRSE. Our findings on the worldwide spread and transmission dynamics of this emerging bacterium has increased the knowledge of its global epidemics. Continued epidemiological surveillance is necessary to prevent global outbreak of multidrug-resistant Salmonella infections.