The role of the st313-td gene in virulence of Salmonella Typhimurium ST313

Multidrug-resistant Salmonella enterica serovar Typhimurium ST313 has emerged in sub-Saharan Africa causing severe infections in humans. Therefore, it has been speculated that this specific sequence type; ST313 carry factors associated with increased pathogenicity. We assessed the role in virulence of the gene with a yet unknown function; st313-td, detected in ST313 through comparative genomics. Additionally, the structure of the genomic island ST313-GI, harbouring the gene was determined. The gene st313-td was cloned into wild type S. Typhimurium #4/74 (#4/74-C) as well as knocked out in S. Typhimurium ST313 #02-03/002 (#02-03/002-KO) followed by complementation (#02-03/002-C). #02-03/002-KO was less virulent in mice following i.p. challenge than the wild type and this phenotype could be complemented in trans, indicating that st313-td plays a role during systemic infection. The gene st313-td was shown not to affect invasion of cultured epithelial cells, while the absence of the gene significantly affect uptake and intracellular survival within macrophages. The gene st313-td was shown to be strongly associated to invasiveness, harboured by 92,5% of S. Typhimurium blood isolates (n=82) and 100% of S. Dublin strains (n=50) analysed. On the contrary, S. Typhimurium isolates of animal and food origin (n=82) did not carry st313-td. Six human, non-blood isolates of S. Typhimurium from Belarus, China, and Nepal harboured the gene and belonged to sequences types ST398 and ST19. Our data showed a global presence of the st313-td gene and in other sequence types than ST313. This study reveals that st313-td plays a role in S. Typhimurium ST313 pathogenesis and adds another chapter to understanding the virulence in S. Typhimurium.