Salmonella enterica subsp. enterica serovar Typhimurium strain:BKQZM9 | isolate:BKQZM9 Genome sequencing

Bloodstream infections caused by invasive non-Typhoidal Salmonella (iNTS) have emerged as a major public health concern in Africa, resulting in ~66,500 deaths every year. The iNTS epidemic has largely been driven by variants of the S. Typhimurium serovar which belong to the sequence type ST313. Two tightly clustered lineages of ST313 exist in Africa (ST313 L1 and ST313 L2), and a more diverse range of ST313 isolates were found in the United Kingdom and Latin America. It has been proposed that antimicrobial resistance (AMR) and genome degradation have contributed to the success of ST313 lineages in Africa, but the evolutionary trajectory of such changes has not been described.Here, we assembled a large and up-to date collection of ST313 isolates from Africa to analyse the stepwise evolution of S. Typhimurium causing BSI. We uncovered an epidemiologically emerging pan-susceptible ST313 lineage (ST313 L3) in Malawi, reflecting the value of changing treatment recommendations in response to AMR. ST313 L3 emerged in Malawi in 2016 and is genetically similar to ST313 variants that cause gastrointestinal disease in the United Kingdom and Brazil. Despite its recent emergence, ST313 L3 represents an evolutionary intermediate between ST313 L1 and the epidemic multidrug resistant ST313 L2. Our in-depth genotypic and phenotypic characterisation identified the crucial loss-of-function genetic events that occurred along the evolutionary pathway of invasive S. Typhimurium across Africa.Together, our data provide an expanded insight into the dynamics of a pathogen responsible for an ongoing epidemic of bloodstream infections and highlights the positive consequence of improved antibiotic stewardship in driving epidemiological shifts in the circulation of Salmonella lineages.