Imperial College London
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Avinash R. Shenoy

Faculty of Medicine, Department of Infectious Disease

Reader in Innate Immunity and Infection
 
 
 
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Contact

 

+44 (0)20 7594 3785a.shenoy Website

 
 
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Location

 

4.40AFlowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@unpublished{Watson:2019:10.1101/799379,
author = {Watson, JL and Sanchez-Garrido, J and Goddard, PJ and Torraca, V and Mostowy, S and Shenoy, AR and Clements, A},
doi = {10.1101/799379},
title = {<i>Shigella sonnei</i>O-antigen inhibits internalisation, vacuole escape and inflammasome activation},
url = {http://dx.doi.org/10.1101/799379},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - UNPB
AB  - <jats:title>Abstract</jats:title><jats:p>Two<jats:italic>Shigella</jats:italic>species,<jats:italic>flexneri</jats:italic>and<jats:italic>sonnei</jats:italic>, cause approximately 90% of bacterial dysentery worldwide. While<jats:italic>S. flexneri</jats:italic>is the dominant species in low-income countries,<jats:italic>S. sonnei</jats:italic>causes the majority of infections in middle and high-income countries.<jats:italic>S. flexneri</jats:italic>is a prototypic cytosolic bacterium; once intracellular it rapidly escapes the phagocytic vacuole and causes pyroptosis of macrophages, which is important for pathogenesis and bacterial spread. By contrast little is known about the invasion, vacuole escape and induction of pyroptosis during<jats:italic>S. sonnei</jats:italic>infection of macrophages. We demonstrate that<jats:italic>S. sonnei</jats:italic>causes substantially less pyroptosis in human primary monocyte-derived macrophages and THP1 cells. This is due to reduced bacterial uptake and lower relative vacuole escape, which results in fewer cytosolic<jats:italic>S. sonnei</jats:italic>and hence reduced activation of caspase-1 inflammasomes. Mechanistically, the O-antigen, which in<jats:italic>S. sonnei</jats:italic>is contained in both the lipopolysaccharide and the capsule, was responsible for reduced uptake and the T3SS was required for vacuole escape. Our findings suggest that<jats:italic>S. sonnei</jats:italic>has adapted to an extracellular lifestyle by incorporating additional O-antigen into its surface structures compared to other<jats:italic>Shigella</jats:italic>species.</jats:p>
AU  - Watson,JL
AU  - Sanchez-Garrido,J
AU  - Goddard,PJ
AU  - Torraca,V
AU  - Mostowy,S
AU  - Shenoy,AR
AU  - Clements,A
DO  - 10.1101/799379
PY  - 2019///
TI  - <i>Shigella sonnei</i>O-antigen inhibits internalisation, vacuole escape and inflammasome activation
UR  - http://dx.doi.org/10.1101/799379
ER  -
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