Bacterial effector NleL promotes enterohemorrhagic E. coli-induced attaching and effacing lesions by ubiquitylating and inactivating JNK

PLoS Pathogens

Ronggui Hu¹  Jinghua Yan²  Qingrun Li³  Rong Zeng⁴  George Fu Gao⁵  Haifeng Wang⁶  Lijian Hui⁷  Kangcheng Ruan⁷  Xiaoduo Xie⁷  Xiangpeng Sheng⁸  Hongnian Zhu⁸  Chen Wang⁸  Feng Shao⁸  Chongtao Du⁸  Dongfang Shi⁸  Hongyan Wang⁸  Anning Lin⁸  Qing You⁹  ZeNan Chang⁹ 

[1] Beijing Institute of microbiology, Chinese Academy of Sciences, Beijing, China;Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois, United States of America;College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, China;College of Veterinary Medicine, Jilin University, Changchun, Jilin, China;College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang, China;David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California, United States of America;State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China;University of Chinese Academy of Sciences, Beijing, China

关键词: Phosphorylation;    Enterohaemorrhagic Escherichia coli;    Immunoprecipitation;    Actins;    HeLa cells;    DAPI staining;    Host cells;    Transfection;   

DOI  :  10.1371/journal.ppat.1006534

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

As a major diarrheagenic human pathogen, enterohemorrhagic Escherichia coli (EHEC) produce attaching and effacing (A/E) lesions, characterized by the formation of actin pedestals, on mammalian cells. A bacterial T3SS effector NleL from EHEC O157:H7 was recently shown to be a HECT-like E3 ligase in vitro, but its biological functions and host targets remain elusive. Here, we report that NleL is required to effectively promote EHEC-induced A/E lesions and bacterial infection. Furthermore, human c-Jun NH2-terminal kinases (JNKs) were identified as primary substrates of NleL. NleL-induced JNK ubiquitylation, particularly mono-ubiquitylation at the Lys 68 residue of JNK, impairs JNK’s interaction with an upstream kinase MKK7, thus disrupting JNK phosphorylation and activation. This subsequently suppresses the transcriptional activity of activator protein-1 (AP-1), which modulates the formation of the EHEC-induced actin pedestals. Moreover, JNK knockdown or inhibition in host cells complements NleL deficiency in EHEC infection. Thus, we demonstrate that the effector protein NleL enhances the ability of EHEC to infect host cells by targeting host JNK, and elucidate an inhibitory role of ubiquitylation in regulating JNK phosphorylation.

【 授权许可】

CC BY