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Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.

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Date
2014-06
Authors
Yan, Qin
Sharma-Kuinkel, Batu K
Deshmukh, Hitesh
Tsalik, Ephraim L
Cyr, Derek D
Lucas, Joseph
Woods, Christopher W
Scott, William K
Sempowski, Gregory D
Thaden, Joshua T
Rude, Thomas H
Ahn, Sun Hee
Fowler, Vance G
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(13 total)
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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 article
Subject
Animals
Animals, 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
Permalink
https://hdl.handle.net/10161/9130
Published Version (Please cite this version)
10.1371/journal.ppat.1004149
Publication 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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Scholars@Duke

Fowler

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
Lucas

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.
Sempowski

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
Thaden

Joshua Thomas Thaden

Assistant Professor of Medicine
Tsalik

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
Woods

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
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