title: The role of the st313-td gene in virulence of Salmonella Typhimurium ST313.
abstract: 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, carries factors associated with increased pathogenicity. We assessed the role in virulence of a 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 (Δst313-td) followed by complementation (02-03/002-C). Δst313-td was less virulent in mice following i.p. challenge than the wild type and this phenotype could be partly 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 affects uptake and intracellular survival within macrophages. The gene st313-td was proven 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 sequence types ST398 and ST19. Our data showed a global presence of the st313-td gene and in other sequence types than ST313. The gene st313-td was shown to be expressed during logarithmic phase of growth in 14 selected Salmonella strains carrying the gene. This study reveals that st313-td plays a role in S. Typhimurium ST313 pathogenesis and adds another chapter to understanding of the virulence of S. Typhimurium and in particular of the emerging sequence type ST313.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark ; WHO Collaborating Centre for Antimicrobial Resistance in Food-borne Pathogens and EU Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Ana
authors.initials: A
authors.lastname: Herrero-Fresno
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: Inke
authors.initials: I
authors.lastname: Wallrodt
authors.affiliation: WHO Collaborating Centre for Antimicrobial Resistance in Food-borne Pathogens and EU Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Pimlapas
authors.initials: P
authors.lastname: Leekitcharoenphon
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
authors.forename: John Elmerdahl
authors.initials: JE
authors.lastname: Olsen
authors.affiliation: WHO Collaborating Centre for Antimicrobial Resistance in Food-borne Pathogens and EU Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Aarestrup
authors.affiliation: WHO Collaborating Centre for Antimicrobial Resistance in Food-borne Pathogens and EU Reference Laboratory for Antimicrobial Resistance, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Rene S
authors.initials: RS
authors.lastname: Hendriksen
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D023061:Gene Order; D016680:Genome, Bacterial; D044404:Genomic Islands; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D058885:Multilocus Sequence Typing; D020641:Polymorphism, Single Nucleotide; D012480:Salmonella Infections / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors