Dusp3 and Psme3 Are Associated with Murine Susceptibility to Staphylococcus aureus Infection and Human Sepsis(PLOS PATHOGENS, 2014, Volume 10(6): e1004149)

報告日期: 2015/03/31
報告時間: 17:10/18:00
報告學生: 許文俐
講評老師: 蔡佩珍
附件下載: 下載[1461-1425857348-1.pdf] 

Topic:Dusp3 and Psme3 Are Associated with Murine Susceptibility to Staphylococcus aureus Infection and Human Sepsis

Date: 2015/03/ 31

Reporter: Hsu Wen-Li

The source: PLOS PATHOGENS Vol. 10, e1004149, 2014

Advisor: Yan Shian-Jang


Sepsis results from the interaction between a host and an invading pathogen. Staphylococcus aureus (S. aureus) is themost common pathogen whose clinical spectrum ranges from asymptomatic colonization to endocarditis, shock, and death. Although it has recently been shown that A/J mice are highly susceptible to S. aureus sepsis as compared to C57BL/6J, the specific genes responsible for this differential phenotype are unknown. To identify genetic determinants of susceptibility for S. aureus and evaluate their function with regard to S. aureus infection, CSS11 (C57BL/6J background with chromosome 11 from A/J) were utilized combining with microarray expression and Quantitative trait loci (QTL) mapping. One QTL region on chromosome 11 containing 422 genes was identified to be significantly associated with susceptibility to S. aureus infection. Of these 422 genes, whole genome transcription profiling classified five genes: Dcaf7, Dusp3, Fam134c, Psme3, and Slc4a1, that were significantly differentially expressed in a) S. aureus –infected susceptible (A/J) comparing with resistant (C57BL/6J) mice and b) humans with S. aureus blood stream infection comparing with healthy subjects. Dcaf7, Dusp3, and Psme3 were down-regulated in susceptible vs. resistant mice at both pre- and post-infection time points by qPCR. Knockdown of Dusp3 and Psme3 by siRNA induced significant enhances of cytokine production in S. aureus-infected RAW264.7 macrophages and bone marrow derived macrophages (BMDMs) via promoting NF-κB signaling activity. Besides, cytokine production and NF-κB activity are also displayed the similar increases in BMDMs from CSS11, but not C57BL/6J. These results indicated that Dusp3 and Psme3 result in S. aureus infection susceptibility in A/J mice and play a role in human S. aureus infection.


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