Imperial College London
Alternate

Dr Abigail Clements

Faculty of Natural Sciences, Department of Life Sciences

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 7681a.clements

 
 
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Location

 

1.42Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Torraca:2019:10.1101/719781,
author = {Torraca, V and Kaforou, M and Watson, J and Duggan, GM and Guerrero-Gutierrez, H and Krokowski, S and Hollinshead, M and Clarke, TB and Mostowy, RJ and Tomlinson, GS and Sancho-Shimizu, V and Clements, A and Mostowy, S},
doi = {10.1101/719781},
title = {<i>Shigella sonnei</i>infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence},
url = {http://dx.doi.org/10.1101/719781},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p><jats:italic>Shigella flexneri</jats:italic>is historically regarded as the primary agent of bacillary dysentery, yet the closely-related<jats:italic>Shigella sonnei</jats:italic>is replacing<jats:italic>S. flexneri</jats:italic>, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (<jats:italic>Danio rerio</jats:italic>) model of<jats:italic>Shigella</jats:italic>infection, we discover that<jats:italic>S. sonnei</jats:italic>is more virulent than<jats:italic>S. flexneri in vivo</jats:italic>. Whole animal dual-RNAseq and testing of bacterial mutants suggest that<jats:italic>S. sonnei</jats:italic>virulence depends on its O-antigen oligosaccharide (which is unique among<jats:italic>Shigella</jats:italic>species). We show<jats:italic>in vivo</jats:italic>using zebrafish and<jats:italic>ex vivo</jats:italic>using human neutrophils that<jats:italic>S. sonnei</jats:italic>O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables<jats:italic>S. sonnei</jats:italic>to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of<jats:italic>S. sonnei</jats:italic>and zebrafish survival. Strikingly, larvae primed with a sublethal dose of<jats:italic>S. sonnei</jats:italic>are protected against a secondary lethal dose of<jats:italic>S. sonnei</jats:italic>in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against<jats:italic>S. sonnei</jats:italic>. Collectively, these findings reveal O-antigen as an important therapeutic
AU  - Torraca,V
AU  - Kaforou,M
AU  - Watson,J
AU  - Duggan,GM
AU  - Guerrero-Gutierrez,H
AU  - Krokowski,S
AU  - Hollinshead,M
AU  - Clarke,TB
AU  - Mostowy,RJ
AU  - Tomlinson,GS
AU  - Sancho-Shimizu,V
AU  - Clements,A
AU  - Mostowy,S
DO  - 10.1101/719781
PY  - 2019///
TI  - <i>Shigella sonnei</i>infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence
UR  - http://dx.doi.org/10.1101/719781
ER  -
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