title: What's in a Name? Species-Wide Whole-Genome Sequencing Resolves Invasive and Noninvasive Lineages of Salmonella enterica Serotype Paratyphi B.
abstract: For 100 years, it has been obvious that Salmonella enterica strains sharing the serotype with the formula 1,4,[5],12:b:1,2-now known as Paratyphi B-can cause diseases ranging from serious systemic infections to self-limiting gastroenteritis. Despite considerable predicted diversity between strains carrying the common Paratyphi B serotype, there remain few methods that subdivide the group into groups that are congruent with their disease phenotypes. Paratyphi B therefore represents one of the canonical examples in Salmonella where serotyping combined with classical microbiological tests fails to provide clinically informative information. Here, we use genomics to provide the first high-resolution view of this serotype, placing it into a wider genomic context of the Salmonella enterica species. These analyses reveal why it has been impossible to subdivide this serotype based upon phenotypic and limited molecular approaches. By examining the genomic data in detail, we are able to identify common features that correlate with strains of clinical importance. The results presented here provide new diagnostic targets, as well as posing important new questions about the basis for the invasive disease phenotype observed in a subset of strains.
  
  
  
  Salmonella enterica strains carrying the serotype Paratyphi B have long been known to possess Jekyll and Hyde characteristics; some cause gastroenteritis, while others cause serious invasive disease. Understanding what makes up the population of strains carrying this serotype, as well as the source of their invasive disease, is a 100-year-old puzzle that we address here using genomics. Our analysis provides the first high-resolution view of this serotype, placing strains carrying serotype Paratyphi B into the wider genomic context of the Salmonella enterica species. This work reveals a history of disease dating back to the middle ages, caused by a group of distinct lineages with various abilities to cause invasive disease. By quantifying the key genomic differences between the invasive and noninvasive populations, we are able to identify key virulence-related targets that can form the basis of simple, rapid, point-of-care tests.
authors.affiliation: Cardiff University School of Biosciences, Cardiff University, Cardiff, United Kingdom Wellcome Trust Sanger Institute, Hinxton, United Kingdom connortr@cardiff.ac.uk.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Connor
authors.affiliation: Cardiff University School of Biosciences, Cardiff University, Cardiff, United Kingdom Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Sian V
authors.initials: SV
authors.lastname: Owen
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Gemma
authors.initials: G
authors.lastname: Langridge
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom.
authors.forename: Steve
authors.initials: S
authors.lastname: Connell
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom.
authors.forename: Satheesh
authors.initials: S
authors.lastname: Nair
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Public Health England, London, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Dallman
authors.affiliation: Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland Department of Biostatistics, University of Oslo, Oslo, Norway.
authors.forename: Jukka
authors.initials: J
authors.lastname: Corander
authors.affiliation: Bacteriology and Enteric Disease Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
authors.forename: Kristine C
authors.initials: KC
authors.lastname: Tabing
authors.affiliation: Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Paris, France.
authors.forename: Simon
authors.initials: S
authors.lastname: Le Hello
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Fookes
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Doublet
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Zhemin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Theresa
authors.initials: T
authors.lastname: Feltwell
authors.affiliation: Public Health England, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellington
authors.affiliation: Instituto de Salud Carlos III, Centro Nacional de Microbiología, Majadahonda, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Herrera
authors.affiliation: Bacteriology and Enteric Disease Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gilmour
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, Tours, France.
authors.forename: Axel
authors.initials: A
authors.lastname: Cloeckaert
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Achtman
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Julian
authors.identifier: 0000-0002-7069-5958
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Norwich Medical School, UEA, Norwich, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: De Pinna
authors.affiliation: Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Paris, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Weill
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom.
authors.forename: Tansy
authors.initials: T
authors.lastname: Peters
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, United Kingdom London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Thomson
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D016680:Genome, Bacterial; D005838:Genotype; D006801:Humans; D010284:Paratyphoid Fever / Q000382:microbiology / Q000662:veterinary; D012484:Salmonella paratyphi B / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D017422:Sequence Analysis, DNA