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Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death

Many Gram-negative bacterial pathogens utilize the type III secretion system (T3SS) to inject virulence factors, named effectors, into host cells. These T3SS effectors manipulate host cellular signaling pathways to facilitate bacterial pathogenesis. Death receptor signaling plays an important role i...

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Autores principales: Xue, Juan, Pan, Xing, Peng, Ting, Duan, Meimei, Du, Lijie, Zhuang, Xiaohui, Cai, Xiaobin, Yi, Xueying, Fu, Yang, Li, Shan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214673/
https://www.ncbi.nlm.nih.gov/pubmed/32432056
http://dx.doi.org/10.3389/fcimb.2020.00197
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author Xue, Juan
Pan, Xing
Peng, Ting
Duan, Meimei
Du, Lijie
Zhuang, Xiaohui
Cai, Xiaobin
Yi, Xueying
Fu, Yang
Li, Shan
author_facet Xue, Juan
Pan, Xing
Peng, Ting
Duan, Meimei
Du, Lijie
Zhuang, Xiaohui
Cai, Xiaobin
Yi, Xueying
Fu, Yang
Li, Shan
author_sort Xue, Juan
collection PubMed
description Many Gram-negative bacterial pathogens utilize the type III secretion system (T3SS) to inject virulence factors, named effectors, into host cells. These T3SS effectors manipulate host cellular signaling pathways to facilitate bacterial pathogenesis. Death receptor signaling plays an important role in eukaryotic cell death pathways. NleB from enteropathogenic Escherichia coli (EPEC) and SseK1/3 from Salmonella enterica serovar Typhimurium (S. Typhimurium) are T3SS effectors. They are defined as a family of arginine GlcNAc transferase to modify a conserved arginine residue in the death domain (DD) of the death receptor TNFR and their corresponding adaptors to hijack death receptor signaling. Here we identified that these enzymes, NleB, SseK1, and SseK3 could catalyze auto-GlcNAcylation. Residues, including Arg13/53/159/293 in NleB, Arg30/158/339 in SseK1, and Arg153/184/305/335 in SseK3 were identified as the auto-GlcNAcylation sites by mass spectrometry. Mutation of the auto-modification sites of NleB, SseK1, and SseK3 abolished or attenuated the capability of enzyme activity toward their death domain targets during infection. Loss of this ability led to the increased susceptibility of the cells to TNF- or TRAIL-induced cell death during bacterial infection. Overall, our study reveals that the auto-GlcNAcylation of NleB, SseK1, and SseK3 is crucial for their biological activity during infection.
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spelling pubmed-72146732020-05-19 Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death Xue, Juan Pan, Xing Peng, Ting Duan, Meimei Du, Lijie Zhuang, Xiaohui Cai, Xiaobin Yi, Xueying Fu, Yang Li, Shan Front Cell Infect Microbiol Cellular and Infection Microbiology Many Gram-negative bacterial pathogens utilize the type III secretion system (T3SS) to inject virulence factors, named effectors, into host cells. These T3SS effectors manipulate host cellular signaling pathways to facilitate bacterial pathogenesis. Death receptor signaling plays an important role in eukaryotic cell death pathways. NleB from enteropathogenic Escherichia coli (EPEC) and SseK1/3 from Salmonella enterica serovar Typhimurium (S. Typhimurium) are T3SS effectors. They are defined as a family of arginine GlcNAc transferase to modify a conserved arginine residue in the death domain (DD) of the death receptor TNFR and their corresponding adaptors to hijack death receptor signaling. Here we identified that these enzymes, NleB, SseK1, and SseK3 could catalyze auto-GlcNAcylation. Residues, including Arg13/53/159/293 in NleB, Arg30/158/339 in SseK1, and Arg153/184/305/335 in SseK3 were identified as the auto-GlcNAcylation sites by mass spectrometry. Mutation of the auto-modification sites of NleB, SseK1, and SseK3 abolished or attenuated the capability of enzyme activity toward their death domain targets during infection. Loss of this ability led to the increased susceptibility of the cells to TNF- or TRAIL-induced cell death during bacterial infection. Overall, our study reveals that the auto-GlcNAcylation of NleB, SseK1, and SseK3 is crucial for their biological activity during infection. Frontiers Media S.A. 2020-05-05 /pmc/articles/PMC7214673/ /pubmed/32432056 http://dx.doi.org/10.3389/fcimb.2020.00197 Text en Copyright © 2020 Xue, Pan, Peng, Duan, Du, Zhuang, Cai, Yi, Fu and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Xue, Juan
Pan, Xing
Peng, Ting
Duan, Meimei
Du, Lijie
Zhuang, Xiaohui
Cai, Xiaobin
Yi, Xueying
Fu, Yang
Li, Shan
Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death
title Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death
title_full Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death
title_fullStr Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death
title_full_unstemmed Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death
title_short Auto Arginine-GlcNAcylation Is Crucial for Bacterial Pathogens in Regulating Host Cell Death
title_sort auto arginine-glcnacylation is crucial for bacterial pathogens in regulating host cell death
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214673/
https://www.ncbi.nlm.nih.gov/pubmed/32432056
http://dx.doi.org/10.3389/fcimb.2020.00197
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