What’s in a Name? Species-Wide Whole-Genome Sequencing Resolves Invasive and Noninvasive Lineages of <named-content content-type="genus-species">Salmonella enterica</named-content> Serotype Paratyphi B
Thomas R. Connor,
Sian V. Owen,
Gemma Langridge,
Steve Connell,
Satheesh Nair,
Sandra Reuter,
Timothy J. Dallman,
Jukka Corander,
Kristine C. Tabing,
Simon Le Hello,
Maria Fookes,
Benoît Doublet,
Zhemin Zhou,
Theresa Feltwell,
Matthew J. Ellington,
Silvia Herrera,
Matthew Gilmour,
Axel Cloeckaert,
Mark Achtman,
Julian Parkhill,
John Wain,
Elizabeth De Pinna,
François-Xavier Weill,
Tansy Peters,
Nick Thomson
Affiliations
Thomas R. Connor
Cardiff University School of Biosciences, Cardiff University, Cardiff, United Kingdom
Sian V. Owen
Cardiff University School of Biosciences, Cardiff University, Cardiff, United Kingdom
Gemma Langridge
Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom
Steve Connell
Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom
Satheesh Nair
Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom
Sandra Reuter
Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Timothy J. Dallman
Public Health England, London, United Kingdom
Jukka Corander
Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland
Kristine C. Tabing
Bacteriology and Enteric Disease Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada
Simon Le Hello
Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Paris, France
Maria Fookes
Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Benoît Doublet
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France
Zhemin Zhou
Warwick Medical School, University of Warwick, Coventry, United Kingdom
Theresa Feltwell
Wellcome Trust Sanger Institute, Hinxton, United Kingdom
Matthew J. Ellington
Public Health England, Addenbrooke’s Hospital, Cambridge, United Kingdom
Silvia Herrera
Instituto de Salud Carlos III, Centro Nacional de Microbiología, Majadahonda, Madrid, Spain
Matthew Gilmour
Bacteriology and Enteric Disease Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada
Axel Cloeckaert
INRA, UMR1282 Infectiologie et Santé Publique, Nouzilly, France
Mark Achtman
Warwick Medical School, University of Warwick, Coventry, United Kingdom
Julian Parkhill
Wellcome Trust Sanger Institute, Hinxton, United Kingdom
John Wain
Norwich Medical School, UEA, Norwich, United Kingdom
Elizabeth De Pinna
Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom
François-Xavier Weill
Institut Pasteur, Unité des Bactéries Pathogènes Entériques, Paris, France
Tansy Peters
Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom
Nick Thomson
Wellcome Trust Sanger Institute, Hinxton, United Kingdom
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. IMPORTANCE 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.