Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.
Abstract
Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to identify
genetic determinants of susceptibility to S. aureus, and evaluate their function with
regard to S. aureus infection. One QTL region on chromosome 11 containing 422 genes
was found to be significantly associated with susceptibility to S. aureus infection.
Of these 422 genes, whole genome transcription profiling identified five genes (Dcaf7,
Dusp3, Fam134c, Psme3, and Slc4a1) that were significantly differentially expressed
in a) S. aureus -infected susceptible (A/J) vs. resistant (C57BL/6J) mice and b) humans
with S. aureus blood stream infection vs. healthy subjects. Three of these genes (Dcaf7,
Dusp3, and Psme3) were down-regulated in susceptible vs. resistant mice at both pre-
and post-infection time points by qPCR. siRNA-mediated knockdown of Dusp3 and Psme3
induced significant increases of cytokine production in S. aureus-challenged RAW264.7
macrophages and bone marrow derived macrophages (BMDMs) through enhancing NF-κB signaling
activity. Similar increases in cytokine production and NF-κB activity were also seen
in BMDMs from CSS11 (C57BL/6J background with chromosome 11 from A/J), but not C57BL/6J.
These findings suggest that Dusp3 and Psme3 contribute to S. aureus infection susceptibility
in A/J mice and play a role in human S. aureus infection.
Type
Journal articleSubject
AnimalsAnimals, Genetically Modified
Autoantigens
Bacteremia
Cell Line, Transformed
Cells, Cultured
Disease Susceptibility
Dual Specificity Phosphatase 3
Female
Gene Expression Regulation
Genome-Wide Association Study
Humans
Immunity, Innate
Macrophages
Male
Mice
Proteasome Endopeptidase Complex
RNA Interference
Recombinant Proteins
Staphylococcal Infections
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https://hdl.handle.net/10161/9130Published Version (Please cite this version)
10.1371/journal.ppat.1004149Publication Info
Yan, Qin; Sharma-Kuinkel, Batu K; Deshmukh, Hitesh; Tsalik, Ephraim L; Cyr, Derek
D; Lucas, Joseph; ... Fowler, Vance G (2014). Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus
infection and human sepsis. PLoS Pathog, 10(6). pp. e1004149. 10.1371/journal.ppat.1004149. Retrieved from https://hdl.handle.net/10161/9130.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Vance Garrison Fowler Jr.
Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial
ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
Joseph E. Lucas
Associate Research Professor in the Social Science Research Institute
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Gregory David Sempowski
Professor in Medicine
Dr. Sempowski earned his PhD in Immunology from the University of Rochester and was
specifically trained in the areas of inflammation, wound healing, and host response
(innate and adaptive). Dr. Sempowski contributed substantially to the field of lung
inflammation and fibrosis defining the roles of pulmonary fibroblast heterogeneity
and CD40/CD40L signaling in regulating normal and pathogenic lung inflammation. During
his postdoctoral training with Dr. Barton F. H
Joshua Thomas Thaden
Assistant Professor of Medicine
Ephraim Tsalik
Adjunct Associate Professor in the Department of Medicine
My research at Duke has focused on understanding the dynamic between host and pathogen
so as to discover and develop host-response markers that can diagnose and predict
health and disease. This new and evolving approach to diagnosing illness has the
potential to significantly impact individual as well as public health considering
the rise of antibiotic resistance.
With any potential infectious disease diagnosis, it is difficult, if not impossible,
to determine at the time of pre
Christopher Wildrick Woods
Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance
for communicable diseases 7. Antimicrobial resistance
Alphabetical list of authors with Scholars@Duke profiles.

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