title: Burkholderia pseudomallei-derived miR-3473 enhances NF-κB via targeting TRAF3 and is associated with different inflammatory responses compared to Burkholderia thailandensis in murine macrophages.
abstract: Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a kind of tropical disease. Burkholderia thailandensis (Bt), with a high sequence similarity to Bp, is thought to be an avirulent organism. Since there are numerous similarities between Bp and Bt, their differences in pathogenesis of host response and related mechanism are still undermined. In recent years, microRNAs have been researched in many diseases, but seldom involved in bacterial infection, bacteria-host interaction or explaining the differences between virulent and avirulent species.
  
  
  
  We found that Bp and Bt had similar phenotypes in terms of intracellular replication, dissemination (reflected by multinucleated giant cell formation), TNF-α release and apoptosis in RAW264.7 macrophages or TC-1 pulmonary cell but in different level. Especially, at the late infection phases (after 12 h post infection), Bp showed faster intracellular growth, stronger cytotoxicity, and higher TNF-α release. After microRNA array analysis, we found some microRNAs were significantly expressed in macrophages treated by Bp. miR-3473 was one of them specifically induced, but not significantly changed in Bt-treated macrophages. In addition, TargetScan suggested that miR-3473 possibly target TRAF3 (TNF receptor-associated factor 3), a well-known negative regulator of the NF-κB pathway, which was probably involved in the TNF-α induction and apoptosis in cells with Bp infection. In vivo, it was found that miR-3473 expression of total lungs cells from Bp-treated was higher than that from Bt-treated mice. And miR-3473 inhibitor was able to decrease the TNF-α release of mice and prolong the survival of mice with Bp infection.
  
  
  
  In sum, miR-3473 plays an important role in the differential pathogenicity of Bp and Bt via miR-3473-TRAF3-TNF-α network, and regulates TNF-α release, cell apoptosis and animal survival after Bp treatment. In this study, we have found a specific microRNA is related to bacterial virulence and provide insight into the mechanism for host-bacteria interaction, which suggests that potential oligonucleotides should be applied against bacterial infection.
authors.affiliation: Department of Clinical Microbiology and Immunology of Southwest Hospital and the College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China.|PLA 161 Hospital, Wuhan, 430014, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Clinical Laboratory, People's Hospital of Sanya, Sanya City, Hainan Province, 572000, People's Republic of China.
authors.forename: Hai
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Clinical Microbiology and Immunology of Southwest Hospital and the College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Clinical Microbiology and Immunology of Southwest Hospital and the College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Clinical Microbiology and Immunology of Southwest Hospital and the College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Clinical Microbiology and Immunology of Southwest Hospital and the College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Ma
authors.affiliation: Department of Clinical Microbiology and Immunology of Southwest Hospital and the College of Medical Laboratory Science, Third Military Medical University, No. 30 Gaotanyan Street, Shapingba District, Chongqing, 400038, People's Republic of China. 371095902@qq.com.
authors.forename: Xuhu
authors.initials: X
authors.lastname: Mao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019117:Burkholderia / Q000378:metabolism* / Q000472:pathogenicity; D019121:Burkholderia Infections / Q000382:microbiology*; D016957:Burkholderia pseudomallei / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D002460:Cell Line; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000096:biosynthesis*; D016328:NF-kappa B / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D048008:TNF Receptor-Associated Factor 3; D014409:Tumor Necrosis Factor-alpha
keywords: Apoptosis; Burkholderia pseudomallei (Bp); Burkholderia thailandensis (Bt); NF-κB; TNF-α; TRAF3; miR-3473