A pathogen-derived effector modulates host glucose metabolism by arginine GlcNAcylation of HIF-1 alpha protein
Xu, Chenxi1,2; Liu, Xing1; Zha, Huangyuan1; Fan, Sijia1; Zhang, Dawei1; Li, Shan3,4; Xiao, Wuhan1,5
2018-08-01
Source PublicationPLOS PATHOGENS
ISSN1553-7366
Volume14Issue:8Pages:1-29
AbstractThe essential role of pathogens in host metabolism is widely recognized, yet the mechanisms by which they affect host physiology remain to be fully defined. Here, we found that NIeB, an enteropathogenic Escherichia coli (EPEC) type III secretion system effector known to possess N-acetylglucosamine (GlcNAc) transferase activity, GlcNAcylates HIF-la, a master regulator of cellular O-2 homeostasis. We determined that NIeB-mediated GlcNAcylation at a conserved arginine 18 (Arg18) at the N-terminus of HIF-1 alpha enhanced HIF-1 alpha transcriptional activity, thereby inducing HIF-1 alpha downstream gene expression to alter host glucose metabolism. The arginine transferase activity of NIeB was required for its enhancement of HIF-1 alpha transactivity and the subsequent effect on glucose metabolism in a mouse model of EPEC infection. In addition, HIF-1 alpha acted as a mediator to transact NIeB-mediated induction of glucose metabolism-associated gene expression under hypoxia. Thus, our results further show a causal link between pathogen infection and host glucose metabolism, and we propose a new mechanism by which this occurs.
SubtypeArticle
DOI10.1371/journal.ppat.1007259
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationStrategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(91631102 ; NSFC(91631102 ; 31830101 ; 31830101 ; 31721005) ; 31721005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(91631102 ; NSFC(91631102 ; 31830101 ; 31830101 ; 31721005) ; 31721005)
Language英语
WOS Research AreaMicrobiology ; Parasitology ; Virology
WOS SubjectMicrobiology ; Parasitology ; Virology
WOS KeywordHYPOXIA-INDUCIBLE FACTOR-1 ; GUT MICROBIOTA ; CELL-DEATH ; TRANSCRIPTIONAL ACTIVITY ; HIF-ALPHA ; EXPRESSION ; BACTERIAL ; CANCER ; BNIP3 ; INFLAMMATION
WOS IDWOS:000443296800042
Funding OrganizationStrategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(91631102 ; NSFC(91631102 ; 31830101 ; 31830101 ; 31721005) ; 31721005) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDA08010208) ; NSFC(91631102 ; NSFC(91631102 ; 31830101 ; 31830101 ; 31721005) ; 31721005)
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/56117
Collection藻类生物学及应用研究中心_水生生物分子与细胞生物学研究中心
Corresponding AuthorXiao, Wuhan
Affiliation1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Hubei Univ Med, Taihe Hosp, Inst Infect & Immun, Shiyan, Peoples R China
4.Huazhong Agr Univ, Coll Life Sci & Technol, Biomed Ctr, Wuhan, Hubei, Peoples R China
5.Minist Agr, Key Lab Aquaculture Dis Control, Wuhan, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Xu, Chenxi,Liu, Xing,Zha, Huangyuan,et al. A pathogen-derived effector modulates host glucose metabolism by arginine GlcNAcylation of HIF-1 alpha protein[J]. PLOS PATHOGENS,2018,14(8):1-29.
APA Xu, Chenxi.,Liu, Xing.,Zha, Huangyuan.,Fan, Sijia.,Zhang, Dawei.,...&Xiao, Wuhan.(2018).A pathogen-derived effector modulates host glucose metabolism by arginine GlcNAcylation of HIF-1 alpha protein.PLOS PATHOGENS,14(8),1-29.
MLA Xu, Chenxi,et al."A pathogen-derived effector modulates host glucose metabolism by arginine GlcNAcylation of HIF-1 alpha protein".PLOS PATHOGENS 14.8(2018):1-29.
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