Enhanced virulence and stress tolerance are signatures of epidemiologically successful Shigella sonnei
Shigellosis is a leading cause of diarrhoeal deaths, with Shigella sonnei increasingly implicated as a dominant agent. S. sonnei is divided into five monophyletic lineages, yet most infections are caused by a few clonal sub-lineages within Lineage 3 that are quite distinct from the widely used Lineage 2 laboratory strain 53G. Factors underlying the success of these globally dominant lineages remain unclear in part due to a lack of complete genome sequences and animal models. Here, we utilise a novel reference collection of representative Lineage 1, 2 and 3 isolates and find that epidemiologically successful S. sonnei harbour fewer genes encoding putative immunogenic components whilst key virulence-associated regions (including the type three secretion system and O-antigen) remain highly conserved. Using a zebrafish infection model, Lineage 3 isolates proved most virulent, driven by increased dissemination and a greater neutrophil response. These isolates also show increased resistance to complement-mediated killing alongside upregulated expression of group four capsule synthesis genes. Consistently, primary human neutrophil infections revealed an increased tolerance to phagosomal killing. Together, our findings link the epidemiological success of S. sonnei to heightened virulence and stress tolerance, and highlight zebrafish as a valuable platform to illuminate factors underlying establishment of epidemiological success.
Authors
- Serge Mostowy (ORCID: https://orcid.org/0000-0002-7286-6503)
- Hannah Painter (ORCID: https://orcid.org/0000-0003-0445-7473)
- David Santillo (ORCID: https://orcid.org/0009-0004-3966-4952)
- Vanessa Sancho‐Shimizu (ORCID: https://orcid.org/0000-0002-3519-0727)
- Claire Jenkins (ORCID: https://orcid.org/0000-0001-8600-9169)
- Vincenzo Torraca (ORCID: https://orcid.org/0000-0001-7340-0249)
- Sydney L. Miles (ORCID: https://orcid.org/0000-0003-2291-4105)
- David A. Cisneros (ORCID: https://orcid.org/0000-0001-9919-0075)
- Andrea Puhar (ORCID: https://orcid.org/0000-0002-9915-002X)
- Kathryn Wright (ORCID: https://orcid.org/0000-0001-6508-3386)
- Kate S. Baker (ORCID: https://orcid.org/0000-0001-5850-1949)
- Abigail Clements (ORCID: https://orcid.org/0000-0003-2285-777X)
- Xosé M. Matanza (ORCID: https://orcid.org/0000-0002-3559-7439)
- Mollie Virgo (ORCID: https://orcid.org/0000-0003-0631-8186)
- Kathryn E. Holt (ORCID: https://orcid.org/0000-0003-3949-2471)
- Ana T. López-Jiménez (ORCID: https://orcid.org/0000-0002-0289-738X)
Institutions
- Queen's University Belfast (GB)
- King's College London (GB)
- University of Cambridge (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Experimental Drug Development Centre (SG)
- UK Health Security Agency (GB)
- Imperial College London (GB)
- Royal College of Paediatrics and Child Health (GB)
- Monash University (AU)
- Umeå University (SE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1038/s41467-025-64057-y
- Citations
- 2
- Primary Topic
- Escherichia coli research studies
- Type
- article
- Field-Weighted Citation Impact
- 3.60
Funders
- London School of Hygiene and Tropical Medicine
- Wellcome Trust
- Directorate for Biological Sciences
- Medical Research Council