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Salmonella enterica serovar Infantis presents an ever-increasing threat to public health because of its spread throughout many countries and association with high levels of antimicrobial resistance (AMR). We analyzed whole-genome sequences of 5,284 Salmonella Infantis strains from 74 countries, isolated during 1989-2020 from a wide variety of human, animal, and food sources, to compare genetic phylogeny, AMR determinants, and plasmid presence. The global Salmonella Infantis population structure diverged into 3 clusters: a North American cluster, a European cluster, and a global cluster. The levels of AMR varied by Salmonella Infantis cluster and by isolation source; 73% of poultry isolates were multidrug resistant, compared with 35% of human isolates. This finding correlated with the presence of the pESI megaplasmid; 71% of poultry isolates contained pESI, compared with 32% of human isolates. This study provides key information for public health teams engaged in reducing the spread of this pathogen.

Salmonella Infantis is presenting an increasing risk to public health. Of particular concern are the reports of pESI, a multidrug resistance (MDR) encoding megaplasmid, in isolates from multiple countries, but little is known about its presence or diversity in South Africa. Whole genome sequences of 387 S . Infantis isolates from South Africa (2004-2020) were analysed for genetic phylogeny, recombination frequency, antimicrobial resistance (AMR) determinants, plasmid presence and overall gene content. The population structure of South African S . Infantis was substantially different to S . Infantis reported elsewhere; only two thirds of isolates belonged to eBG31, while the remainder were identified as eBG297, a much rarer group globally. Significantly higher levels of recombination were observed in the eBG297 isolates, which was associated with the presence of prophages. The majority of isolates were putatively susceptible to antimicrobials (335/387) and lacked any plasmids (311/387); the megaplasmid pESI was present in just one isolate. A larger proportion of eBG31 isolates, 19% (49/263), contained at least one AMR determinant, compared to eBG297 at 2% (3/124). Comparison of the pan-genomes of isolates from either eBG identified 943 genes significantly associated with eBG, with 43 found exclusively in eBG31 isolates and 34 in eBG297 isolates. This, along with the single nucleotide polymorphism distance and difference in resistance profiles, suggests that eBG31 and eBG297 isolates occupy different niches within South Africa. If antibiotic-resistant S . Infantis emerges in South Africa, probably through the spread of the pESI plasmid, treatment of this infection would be compromised., Competing Interests: The authors declare that there are no conflicts of interest., (© 2022 The Authors.)