| 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 | |
| Corresponding Author | Xiao, Wuhan(w-xiao@ihb.ac.cn) |
| 2018-08-01 | |
| Source Publication | PLOS PATHOGENS
 |
| ISSN | 1553-7366 |
| Volume | 14Issue:8Pages:29 |
| Abstract | The 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. |
| DOI | 10.1371/journal.ppat.1007259 |
| Funding Organization | Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC |
| Indexed By | SCI ; SCI |
| Language | 英语 |
| Funding Project | Strategic Priority Research Program of the Chinese Academy of Sciences[XDA08010208] ; NSFC[91631102] ; NSFC[31830101] ; NSFC[31721005] |
| WOS Research Area | Microbiology ; Parasitology ; Virology |
| WOS Subject | Microbiology ; Parasitology ; Virology |
| WOS ID | WOS:000443296800042 |
| WOS Keyword | HYPOXIA-INDUCIBLE FACTOR-1 ; GUT MICROBIOTA ; CELL-DEATH ; TRANSCRIPTIONAL ACTIVITY ; HIF-ALPHA ; EXPRESSION ; BACTERIAL ; CANCER ; BNIP3 ; INFLAMMATION |
| Publisher | PUBLIC LIBRARY SCIENCE |
| Funding Organization | Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; NSFC ; NSFC ; NSFC ; NSFC |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://ir.ihb.ac.cn/handle/342005/29443 |
| Collection | 水环境工程研究中心_期刊论文 |
| Corresponding Author | Xiao, Wuhan |
| Affiliation | 1.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):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),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):29. |
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