title: An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid.
abstract: The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.|Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Vanessa K
authors.initials: VK
authors.lastname: Wong
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.|Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, Oxford University, Oxford, UK.|Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: Cardiff University School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Connor
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Pickard
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Page
authors.affiliation: Public Health Laboratory London, Public Health England, London, UK.
authors.forename: Jayshree
authors.initials: J
authors.lastname: Dave
authors.affiliation: Public Health Laboratory London, Public Health England, London, UK.
authors.forename: Niamh
authors.initials: N
authors.lastname: Murphy
authors.affiliation: Public Health Laboratory London, Public Health England, London, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Holliman
authors.affiliation: Division of Infection, Barts Health NHS Trust, London, UK.
authors.forename: Armine
authors.initials: A
authors.lastname: Sefton
authors.affiliation: Division of Infection, Barts Health NHS Trust, London, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Millar
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Zoe A
authors.identifier: 0000-0002-8887-3492
authors.initials: ZA
authors.lastname: Dyson
authors.affiliation: The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Parkville, Victoria 3010, Australia.|Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Kathryn E
authors.identifier: 0000-0003-3949-2471
authors.initials: KE
authors.lastname: Holt
mesh_terms: D016000:Cluster Analysis; D004269:DNA, Bacterial; D005838:Genotype; D005843:Geography; D006239:Haplotypes; D006801:Humans; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012485:Salmonella typhi / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*; D014435:Typhoid Fever / Q000382:microbiology*
chemical_list: D004269:DNA, Bacterial