Data · dataset · 2019
Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence
Listed in LSHTM Data Compass
Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries.
Description
The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo.
Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death.
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Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries.
Links
Where it is published
- DOI doi.org/10.1371/journal.ppat.1008006.s007 ↗
DOI / persistent id · from lshtm ac uk
Catalogue records · 1
- OAI-PMH record datacompass.lshtm.ac.uk/cgi/oai2?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3… ↗
metadata API · from lshtm ac uk
Topics
- From keywords
- Earth & Environmental Science · Humanities · Life Sciences · Medicine & Health · Social Science
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| LSHTM Data Compass | oai:datacompass.lshtm.ac.uk:3207 | 9 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| concepts[field].local:field:earth-environmental | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:humanities | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:medicine-health | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| concepts[field].local:field:social-science | mapping · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| description | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | /metadata/dc/description |
| publication_date | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | |
| title | source · lshtm ac uk | connector:lshtm_ac_uk@1.0.0 | /metadata/dc/title |