Imperial College London
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DrTeresaThurston

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer in Molecular Microbiology
 
 
 
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Contact

 

+44 (0)20 7594 3072t.thurston

 
 
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Location

 

2.40Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{O'Neill:2016:10.1128/mBio.00020-16,
author = {O'Neill, A and Thurston, T and Holden, D},
doi = {10.1128/mBio.00020-16},
journal = {mBio},
title = {Cytosolic Replication of Group A Streptococcus in Human Macrophages},
url = {http://dx.doi.org/10.1128/mBio.00020-16},
volume = {7},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - As key components of innate immune defense, macrophages are essential in controlling bacterial pathogens, includinggroup A Streptococcus (GAS). Despite this, only a limited number of studies have analyzed the recovery of GAS from withinhuman neutrophils and macrophages. Here, we determined the intracellular fate of GAS in human macrophages by using severalquantitative approaches. In both U937 and primary human macrophages, the appearance over time of long GAS chains revealedthat despite GAS-mediated cytotoxicity, replication occurred in viable, propidium iodide-negative macrophages. Whereas themajor virulence factor M1 did not contribute to bacterial growth, a GAS mutant strain deficient in streptolysin O (SLO) was impairedfor intracellular replication. SLO promoted bacterial escape from the GAS-containing vacuole (GCV) into the macrophagecytosol. Up to half of the cytosolic GAS colocalized with ubiquitin and p62, suggesting that the bacteria were targeted bythe autophagy machinery. Despite this, live imaging of U937 macrophages revealed proficient replication of GAS after GCV rupture,indicating that escape from the GCV is important for growth of GAS in macrophages. Our results reveal that GAS can replicatewithin viable human macrophages, with SLO promoting GCV escape and cytosolic growth, despite the recruitment of autophagyreceptors to bacteria.
AU  - O'Neill,A
AU  - Thurston,T
AU  - Holden,D
DO  - 10.1128/mBio.00020-16
PY  - 2016///
SN  - 2161-2129
TI  - Cytosolic Replication of Group A Streptococcus in Human Macrophages
T2  - mBio
UR  - http://dx.doi.org/10.1128/mBio.00020-16
UR  - http://hdl.handle.net/10044/1/30670
VL  - 7
ER  -
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