title: Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri.
abstract: Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence.
authors.affiliation: Cardiff School of Biosciences, Cardiff, United Kingdom.
authors.forename: Thomas R
authors.identifier: http://orcid.org/0000-0003-2394-6504
authors.initials: TR
authors.lastname: Connor
authors.affiliation: Cardiff School of Biosciences, Cardiff, United Kingdom.
authors.forename: Clare R
authors.initials: CR
authors.lastname: Barker
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Centre, Cambridge, United Kingdom.
authors.forename: Kate S
authors.initials: KS
authors.lastname: Baker
authors.affiliation: Unité des Bactéries Pathogènes Entériques, Institut Pasteur, Paris, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Weill
authors.affiliation: Centre for Food and Water Borne Diseases, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Kaisar Ali
authors.initials: KA
authors.lastname: Talukder
authors.affiliation: Centre for Enteric Diseases, National Institute for Communicable Diseases and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Smith
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Stephen
authors.initials: S
authors.lastname: Baker
authors.affiliation: Unité des Bactéries Pathogènes Entériques, Institut Pasteur, Paris, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Gouali
authors.affiliation: The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
authors.forename: Duy
authors.initials: D
authors.lastname: Pham Thanh
authors.affiliation: Centre for Food and Water Borne Diseases, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Ishrat
authors.initials: I
authors.lastname: Jahan Azmi
authors.affiliation: Department of Genetics, Evolution, and Bioagents, Institute of Biology, University of Campinas, São Paulo, Brazil.
authors.forename: Wanderley
authors.initials: W
authors.lastname: Dias da Silveira
authors.affiliation: Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie University, Berlin, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Semmler
authors.affiliation: Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie University, Berlin, Germany.
authors.forename: Lothar H
authors.initials: LH
authors.lastname: Wieler
authors.affiliation: Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Jenkins
authors.affiliation: Global Evaluative Sciences, Inc., Seattle, United States.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cravioto
authors.affiliation: Centre for Food and Water Borne Diseases, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh.
authors.forename: Shah M
authors.initials: SM
authors.lastname: Faruque
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Centre, Cambridge, United Kingdom.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Department of Pharmacy, School of Pharmacy, Hanyang University, Ansan, Republic of Korea.
authors.forename: Dong
authors.initials: D
authors.lastname: Wook Kim
authors.affiliation: Centre for Enteric Diseases, National Institute for Communicable Diseases and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Keddy
authors.affiliation: Pathogen Genomics, Wellcome Trust Sanger Centre, Cambridge, United Kingdom.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Thomson
mesh_terms: D024881:Drug Resistance, Bacterial; D004405:Dysentery, Bacillary / Q000453:epidemiology* / Q000382:microbiology*; D014644:Genetic Variation; D016680:Genome, Bacterial; D014943:Global Health; D006801:Humans; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D058974:Phylogeography; D017422:Sequence Analysis, DNA; D065288:Serogroup; D012763:Shigella flexneri / Q000145:classification* / Q000235:genetics*; D062211:Spatio-Temporal Analysis; D037521:Virulence Factors / Q000235:genetics
chemical_list: D037521:Virulence Factors
keywords: E. coli; Shigella; dysentery; epidemiology; genomics; global health; infectious disease; microbiology; pathogen evolution