Imperial College London
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DrMatthewSiggins

Faculty of Medicine, National Heart & Lung Institute

Research Fellow
 
 
 
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Contact

 

m.siggins Website

 
 
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Location

 

345Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sharma:2019:10.1128/mSphere.00665-19,
author = {Sharma, H and Turner, CE and Siggins, MK and El-Bahrawy, M and Pichon, B and Kearns, A and Sriskandan, S},
doi = {10.1128/mSphere.00665-19},
journal = {mSphere},
title = {Toxic shock syndrome toxin-1 evaluation and antibiotic impact in a transgenic model of staphylococcal soft tissue infection},
url = {http://dx.doi.org/10.1128/mSphere.00665-19},
volume = {4},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Nonmenstrual toxic shock syndrome (nmTSS), linked to TSST-1-producing CC30 Staphylococcus aureus, is the leading manifestation of toxic shock syndrome (TSS). Due to case rarity and a lack of tractable animal models, TSS pathogenesis is poorly understood. We developed an S. aureus abscess model in HLA class II transgenic mice to investigate pathogenesis and treatment. TSST-1 sensitivity was established using murine spleen cell proliferation assays and cytokine assays following TSST-1 injection in vivo. HLA-DQ8 mice were infected subcutaneously with a tst-positive CC30 methicillin-sensitive S. aureus clinical TSS-associated isolate. Mice received intraperitoneal flucloxacillin, clindamycin, flucloxacillin and clindamycin, or a control reagent. Abscess size, bacterial counts, TSST-1 expression, and TSST-1 bioactivity were measured in tissues. Antibiotic effects were compared with the effects of control reagent. Purified TSST-1 expanded HLA-DQ8 T-cell Vβ subsets 3 and 13 in vitro and instigated cytokine release in vivo, confirming TSST-1 sensitivity. TSST-1 was detected in abscesses (0 to 8.0 μg/ml) and draining lymph nodes (0 to 0.2 μg/ml) of infected mice. Interleukin 6 (IL-6), gamma interferon (IFN-γ), KC (CXCL1), and MCP-1 were consistent markers of inflammation during infection. Clindamycin-containing antibiotic regimens reduced abscess size and TSST-1 production. Infection led to detectable TSST-1 in soft tissues, and TSST-1 was detected in draining lymph nodes, events which may be pivotal to TSS pathogenesis. The reduction in TSST-1 production and lesion size after a single dose of clindamycin underscores a potential role for adjunctive clindamycin at the start of treatment of patients suspected of having TSS to alter disease progression.
AU  - Sharma,H
AU  - Turner,CE
AU  - Siggins,MK
AU  - El-Bahrawy,M
AU  - Pichon,B
AU  - Kearns,A
AU  - Sriskandan,S
DO  - 10.1128/mSphere.00665-19
PY  - 2019///
SN  - 2379-5042
TI  - Toxic shock syndrome toxin-1 evaluation and antibiotic impact in a transgenic model of staphylococcal soft tissue infection
T2  - mSphere
UR  - http://dx.doi.org/10.1128/mSphere.00665-19
UR  - http://hdl.handle.net/10044/1/73671
VL  - 4
ER  -
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