Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.
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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.
Animals, Genetically Modified
Cell Line, Transformed
Dual Specificity Phosphatase 3
Gene Expression Regulation
Genome-Wide Association Study
Proteasome Endopeptidase Complex
Published Version (Please cite this version)10.1371/journal.ppat.1004149
Publication InfoAhn, SH; Cyr, Derek; Deshmukh, H; Fowler, Vance Garrison Jr; Lucas, J; Rude, Thomas H; ... Yan, Q (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.
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Florence McAlister Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Pathogenesis of Bacterial Infections Infections due to Resistant Gram Positive Organisms Tropical medicine/International Health
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
Assistant Professor of Medicine
Associate Professor of Medicine
My research is 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 presentation
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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