Metalloprotease NleC suppresses host NF-κB/inflammatory responses by cleaving p65 and interfering with the p65/RPS3 interaction

PLoS Pathogens
Andrea HodgsonFengyi Wan

Abstract

Attaching/Effacing (A/E) pathogens including enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC) and the rodent equivalent Citrobacter rodentium are important causative agents of foodborne diseases. Upon infection, a myriad of virulence proteins (effectors) encoded by A/E pathogens are injected through their conserved type III secretion systems (T3SS) into host cells where they interfere with cell signaling cascades, in particular the nuclear factor kappaB (NF-κB) signaling pathway that orchestrates both innate and adaptive immune responses for host defense. Among the T3SS-secreted non-LEE-encoded (Nle) effectors, NleC, a metalloprotease, has been recently elucidated to modulate host NF-κB signaling by cleaving NF-κB Rel subunits. However, it remains elusive how NleC recognizes NF-κB Rel subunits and how the NleC-mediated cleavage impacts on host immune responses in infected cells and animals. In this study, we show that NleC specifically targets p65/RelA through an interaction with a unique N-terminal sequence in p65. NleC cleaves p65 in intestinal epithelial cells, albeit a small percentage of the molecule, to generate the p65¹⁻³⁸ fragment during C. rodentium infection in cultured cells. Moreover, the N...Continue Reading

References

Nov 7, 1995·Proceedings of the National Academy of Sciences of the United States of America·I AlkalayY Ben-Neriah
Mar 1, 1997·Trends in Microbiology·M S DonnenbergB B Finlay
Jun 10, 1998·Microbiology and Molecular Biology Reviews : MMBR·C J Hueck
Dec 26, 2001·Diagnostic Microbiology and Infectious Disease·S C Clarke
Apr 24, 2002·The Journal of Biological Chemistry·Benjamin BerkowitzGourisankar Ghosh
May 30, 2003·The EMBO Journal·M Gabriella SantoroCarla Amici
Feb 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Wanyin DengB Brett Finlay
Mar 26, 2004·Nature Reviews. Microbiology·James B KaperHarry L Mobley
Aug 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pamela CameronRobin Plevin
Sep 17, 2004·Genes & Development·Matthew S Hayden, Sankar Ghosh
Dec 14, 2004·Microbiology and Molecular Biology Reviews : MMBR·Partho Ghosh
Apr 23, 2005·The Journal of Biological Chemistry·Nickolay NeznanovAndrei V Gudkov
Nov 29, 2005·Cellular Microbiology·Rosanna MundySiouxsie Wiles
Mar 7, 2006·PLoS Pathogens·Masmudur M Rahman, Grant McFadden
Apr 6, 2006·Journal of Medical Microbiology·Andréa Vieira ColomboAna Paula Vieira Colombo
Aug 5, 2006·Journal of Leukocyte Biology·Joseph E QuallsDonald A Cohen
Sep 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Toru TobeMark J Pallen
Feb 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sonya P LadErguang Li
Oct 16, 2007·Clinical Microbiology Reviews·Bryan CoburnB Brett Finlay
Mar 24, 2009·Annual Review of Immunology·Sivakumar Vallabhapurapu, Michael Karin
Jul 8, 2009·The Journal of Experimental Medicine·Emily J CaderaMark S Schlissel
Aug 27, 2009·American Journal of Physiology. Endocrinology and Metabolism·Dariush MokhtariNils Welsh
Dec 26, 2009·The Journal of Biological Chemistry·Wanyin DengB Brett Finlay
Dec 31, 2009·PLoS Pathogens·Xiaofei GaoPhilip R Hardwidge
Jan 2, 2010·Current Opinion in Microbiology·David O'Callaghan, C Erec Stebbins
Jan 9, 2010·Advances in Experimental Medicine and Biology·Orla MulhernAndrew G Bowie
Jan 13, 2010·Cold Spring Harbor Perspectives in Biology·Fengyi Wan, Michael J Lenardo
Feb 4, 2010·PLoS Pathogens·Chen NadlerIlan Rosenshine
Sep 14, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna VossenkämperThomas T MacDonald
Nov 26, 2010·Molecular Microbiology·Sandhya V RoyanGail A Hecht
Nov 30, 2010·The EMBO Journal·Kobi BaruchIlan Rosenshine
Dec 18, 2010·Bulletin of Experimental Biology and Medicine·V A ChereshnevI B Ivshina

❮ Previous
Next ❯

Citations

Feb 13, 2016·Frontiers in Microbiology·Ana do ValeSandra Sousa
Jan 18, 2018·Infection and Immunity·Maarten F de Jong, Neal M Alto
Dec 21, 2019·Antioxidants & Redox Signaling·Sergio Rius-PérezJuan Sastre
May 21, 2020·Journal of Burn Care & Research : Official Publication of the American Burn Association·Xingtang NiuQing Tang
Jun 23, 2015·Cellular Microbiology·Cristina GioghaElizabeth L Hartland
Apr 30, 2017·Frontiers in Cellular and Infection Microbiology·Anne-Sophie StolleM Alexander Schmidt
Jul 28, 2020·Future Microbiology·Anna Katharina Riebisch, Sabrina Mühlen
Jun 3, 2021·Pathogens·Md Kamrul HasanPhilip R Hardwidge
Aug 16, 2021·Cellular Microbiology·Flávia VianaGunnar N Schroeder
Sep 24, 2021·ACS Chemical Biology·Ashweta Sahni, Dehua Pei
Jul 20, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Li LuoFu-Yang Pei

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
ubiquitination
protease
pull-down
cleavage assay
PCR
immunoprecipitation
pulldown
transfection

Software Mentioned

GraphPad
Pymol
GraphPad Prism
ImageJ

Related Concepts

Related Feeds

Botulism (ASM)

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

Botulism

Botulism is a rare but serious paralytic illness caused by a nerve toxin that is produced by the bacterium clostridium botulinum. Discover the latest research on botulism here.

Advanced Imaging of Cellular Signaling

Cell signaling is a vital mechanism for communication within cells and outside with the environment. Several different signaling pathways have been found and advanced imaging techniques are being developed to visualize the molecules involved in these signaling pathways. Find the latest research in advanced imaging of cellular signaling here.