Toxic shock syndrome toxin-1 evaluation and antibiotic impact in a transgenic model of staphylococcal soft tissue infection
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2019-10-09
Date Acceptance
2019-09-23
Citation
mSphere, 2019, 4 (5)
ISSN
2379-5042
Publisher
American Society for Microbiology
Journal / Book Title
mSphere
Volume
4
Issue
5
Copyright Statement
© 2019 Sharma et al.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/).
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Grant Number
G0800777
G0800777
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
antibiotics
dissemination
HLA-DQ8
nonmenstrual toxic shock syndrome
Staphylococcus aureus
TSST-1
transgenic mice
PANTON-VALENTINE LEUKOCIDIN
T-CELLS
IMMUNE-RESPONSE
SUPERANTIGEN
MICE
POLYMORPHISMS
ENTEROTOXINS
STIMULATION
MURINE
ALPHA
HLA-DQ8
Staphylococcus aureus
TSST-1
antibiotics
dissemination
nonmenstrual toxic shock syndrome
transgenic mice
Publication Status
Published
Article Number
e00665-19
Date Publish Online
2019-10-09