Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri

Author:

Connor Thomas R12ORCID,Barker Clare R1,Baker Kate S2,Weill François-Xavier3,Talukder Kaisar Ali4,Smith Anthony M5,Baker Stephen678,Gouali Malika3,Pham Thanh Duy678,Jahan Azmi Ishrat4,Dias da Silveira Wanderley9,Semmler Torsten1011,Wieler Lothar H1011,Jenkins Claire12,Cravioto Alejandro13,Faruque Shah M4,Parkhill Julian2,Wook Kim Dong14,Keddy Karen H5,Thomson Nicholas R28

Affiliation:

1. Cardiff School of Biosciences, Cardiff, United Kingdom

2. Pathogen Genomics, Wellcome Trust Sanger Centre, Cambridge, United Kingdom

3. Unité des Bactéries Pathogènes Entériques, Institut Pasteur, Paris, France

4. Centre for Food and Water Borne Diseases, International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh

5. Centre for Enteric Diseases, National Institute for Communicable Diseases and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

6. The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam

7. Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom

8. The London School of Hygiene and Tropical Medicine, London, United Kingdom

9. Department of Genetics, Evolution, and Bioagents, Institute of Biology, University of Campinas, São Paulo, Brazil

10. Centre for Infection Medicine, Institute of Microbiology and Epizootics, Freie University, Berlin, Germany

11. Robert Koch Institute, Berlin, Germany

12. Gastrointestinal Bacteria Reference Unit, Public Health England, London, United Kingdom

13. Global Evaluative Sciences, Inc., Seattle, United States

14. Department of Pharmacy, School of Pharmacy, Hanyang University, Ansan, Republic of Korea

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.

Funder

Wellcome Trust

Medical Research Council (MRC)

Cardiff University

Institut Pasteur

Institut de veille sanitaire

Government of the French Republic

National Research Foundation of Korea

Wellcome Trust/National Institute for Social Care and Health Research ISSF grant to Cardiff University

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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