Shigella Serotypes Associated With Carriage in Humans Establish Persistent Infection in Zebrafish

Author:

Torraca Vincenzo123ORCID,Brokatzky Dominik1ORCID,Miles Sydney L1ORCID,Chong Charlotte E4,De Silva P Malaka4,Baker Stephen5ORCID,Jenkins Claire6,Holt Kathryn E17ORCID,Baker Kate S48ORCID,Mostowy Serge1ORCID

Affiliation:

1. Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom

2. School of Life Sciences, University of Westminster , London, United Kingdom

3. Department of Infectious Diseases, School of Immunology and Microbial Sciences, King’s College London, London, United Kingdom

4. Clinical Infection, Microbiology, and Immunology, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom

5. Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom

6. Gastrointestinal Bacterial Reference Unit, UK Health Security Agency, London, United Kingdom

7. Department of Infectious Diseases, Central Clinical School, Monash University , Melbourne , Australia

8. Department of Genetics, University of Cambridge, Cambridge, United Kingdom

Abstract

Abstract Shigella represents a paraphyletic group of enteroinvasive Escherichia coli. More than 40 Shigella serotypes have been reported. However, most cases within the men who have sex with men (MSM) community are attributed to 3 serotypes: Shigella sonnei unique serotype and Shigella flexneri 2a and 3a serotypes. Using the zebrafish model, we demonstrate that Shigella can establish persistent infection in vivo. Bacteria are not cleared by the immune system and become antibiotic tolerant. Establishment of persistent infection depends on the O-antigen, a key constituent of the bacterial surface and a serotype determinant. Representative isolates associated with MSM transmission persist in zebrafish, while representative isolates of a serotype not associated with MSM transmission do not. Isolates of a Shigella serotype establishing persistent infections elicited significantly less macrophage death in vivo than isolates of a serotype unable to persist. We conclude that zebrafish are a valuable platform to illuminate factors underlying establishment of Shigella persistent infection in humans.

Funder

London School of Hygiene and Tropical Medicine/Wellcome

Trust Institutional Strategic Support Fund

Biotechnology and Biological Sciences Research Council

Deutsche Forschungsgemeinschaft

Walter Benjamin Programme

Academy of Medical Sciences

Medical Research Council New Investigator

European Research Council Consolidator Grant

Wellcome Trust Senior Research Fellowship

Lister Institute of Preventive Medicine

National Institute for Health Research Health Protection Research Unit

Gastrointestinal Infections

University of Liverpool

United Kingdom Health Security Agency

University of Warwick

Department of Health and Social Care

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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