Enterohemorrhagic E. coli effector NleL disrupts host NF-κB signaling by targeting multiple host proteins

作者：Xiangpeng Sheng, Qing You, Hongnian Zhu, Qingrun Li, Hong Gao, Haifeng Wang, Chunping You, Qing Meng, Yingjie Nie, Xiangyan Zhang, Ronggui Hu · 发表于：Journal of Molecular Cell Biology · 年份：2020 · DOI：10.1093/jmcb/mjaa003 · 被引用次数：13 · 研究领域：Escherichia coli research studies、Viral gastroenteritis research and epidemiology、Antibiotic Resistance in Bacteria

Dear Editor, Enterohemorrhagic Escherichia coli (EHEC) O157:H7, a major diarrheagenic pathogen, can cause bloody diarrhea, hemorrhagic colitis, and >90% of hemolytic uremic syndrome in humans (Mead and Griffin, 1998). Many previous studies have demonstrated that O157:H7 could disrupt host ubiquitin (Ub) system by delivering virulence effectors into host cells with the type III secretion system (T3SS). NleL (also named EspX7) emerged as one of such effectors, whose E3-like activity was first identified in vitro in 2011 (Lin et al., 2011). Our recent work revealed that NleL ubiquitylates human JNK proteins and promotes EHEC-associated A/E lesions (Sheng et al., 2017). However, it remains undetermined whether NleL might mediate other microbe–host interactions that contribute to EHEC infection. Here, we demonstrate that NleL targets several components of the NF-κB pathway to suppress host NF-κB activation. As the NF-κB pathway is a major target for many bacterial effectors (Neish and Naumann, 2011), we systematically studied the impact of NleL on NF-κB signaling. First, the ectopic expression of NleL in HEK293T cells was shown to dramatically suppress TNFα-mediated p65 phosphorylation (Figure 1A). NleL also attenuated IKK phosphorylation and IκBα degradation (Figure 1A). Second, we found that EGFP-fused NleL, but not EGFP alone, disrupted the nuclear translocation of p65 in response to TNFα, though they have similar localization in HeLa cells at rest (Figure 1B; Supplementary Fig...