The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.

To further its pathogenesis, S. Typhimurium delivers effector proteins into host cells, including the novel E3 ubiquitin ligase (NEL) effector SspH2. Using model systems in a cross-kingdom approach we gained further insight into the molecular function of this effector. Here, we show that SspH2 modul...

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Autores principales: Amit P Bhavsar, Nat F Brown, Jan Stoepel, Marcel Wiermer, Dale D O Martin, Karolynn J Hsu, Koshi Imami, Colin J Ross, Michael R Hayden, Leonard J Foster, Xin Li, Phil Hieter, B Brett Finlay
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/18d8300ef9bc4b3f815eb0cf4287600f
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spelling oai:doaj.org-article:18d8300ef9bc4b3f815eb0cf4287600f2021-11-18T06:07:51ZThe Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.1553-73661553-737410.1371/journal.ppat.1003518https://doaj.org/article/18d8300ef9bc4b3f815eb0cf4287600f2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935490/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374To further its pathogenesis, S. Typhimurium delivers effector proteins into host cells, including the novel E3 ubiquitin ligase (NEL) effector SspH2. Using model systems in a cross-kingdom approach we gained further insight into the molecular function of this effector. Here, we show that SspH2 modulates innate immunity in both mammalian and plant cells. In mammalian cell culture, SspH2 significantly enhanced Nod1-mediated IL-8 secretion when transiently expressed or bacterially delivered. In addition, SspH2 also enhanced an Rx-dependent hypersensitive response in planta. In both of these nucleotide-binding leucine rich repeat receptor (NLR) model systems, SspH2-mediated phenotypes required its catalytic E3 ubiquitin ligase activity and interaction with the conserved host protein SGT1. SGT1 has an essential cell cycle function and an additional function as an NLR co-chaperone in animal and plant cells. Interaction between SspH2 and SGT1 was restricted to SGT1 proteins that have NLR co-chaperone function and accordingly, SspH2 did not affect SGT1 cell cycle functions. Mechanistic studies revealed that SspH2 interacted with, and ubiquitinated Nod1 and could induce Nod1 activity in an agonist-independent manner if catalytically active. Interestingly, SspH2 in vitro ubiquitination activity and protein stability were enhanced by SGT1. Overall, this work adds to our understanding of the sophisticated mechanisms used by bacterial effectors to co-opt host pathways by demonstrating that SspH2 can subvert immune responses by selectively exploiting the functions of a conserved host co-chaperone.Amit P BhavsarNat F BrownJan StoepelMarcel WiermerDale D O MartinKarolynn J HsuKoshi ImamiColin J RossMichael R HaydenLeonard J FosterXin LiPhil HieterB Brett FinlayPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 7, p e1003518 (2013)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Amit P Bhavsar
Nat F Brown
Jan Stoepel
Marcel Wiermer
Dale D O Martin
Karolynn J Hsu
Koshi Imami
Colin J Ross
Michael R Hayden
Leonard J Foster
Xin Li
Phil Hieter
B Brett Finlay
The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.
description To further its pathogenesis, S. Typhimurium delivers effector proteins into host cells, including the novel E3 ubiquitin ligase (NEL) effector SspH2. Using model systems in a cross-kingdom approach we gained further insight into the molecular function of this effector. Here, we show that SspH2 modulates innate immunity in both mammalian and plant cells. In mammalian cell culture, SspH2 significantly enhanced Nod1-mediated IL-8 secretion when transiently expressed or bacterially delivered. In addition, SspH2 also enhanced an Rx-dependent hypersensitive response in planta. In both of these nucleotide-binding leucine rich repeat receptor (NLR) model systems, SspH2-mediated phenotypes required its catalytic E3 ubiquitin ligase activity and interaction with the conserved host protein SGT1. SGT1 has an essential cell cycle function and an additional function as an NLR co-chaperone in animal and plant cells. Interaction between SspH2 and SGT1 was restricted to SGT1 proteins that have NLR co-chaperone function and accordingly, SspH2 did not affect SGT1 cell cycle functions. Mechanistic studies revealed that SspH2 interacted with, and ubiquitinated Nod1 and could induce Nod1 activity in an agonist-independent manner if catalytically active. Interestingly, SspH2 in vitro ubiquitination activity and protein stability were enhanced by SGT1. Overall, this work adds to our understanding of the sophisticated mechanisms used by bacterial effectors to co-opt host pathways by demonstrating that SspH2 can subvert immune responses by selectively exploiting the functions of a conserved host co-chaperone.
format article
author Amit P Bhavsar
Nat F Brown
Jan Stoepel
Marcel Wiermer
Dale D O Martin
Karolynn J Hsu
Koshi Imami
Colin J Ross
Michael R Hayden
Leonard J Foster
Xin Li
Phil Hieter
B Brett Finlay
author_facet Amit P Bhavsar
Nat F Brown
Jan Stoepel
Marcel Wiermer
Dale D O Martin
Karolynn J Hsu
Koshi Imami
Colin J Ross
Michael R Hayden
Leonard J Foster
Xin Li
Phil Hieter
B Brett Finlay
author_sort Amit P Bhavsar
title The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.
title_short The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.
title_full The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.
title_fullStr The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.
title_full_unstemmed The Salmonella type III effector SspH2 specifically exploits the NLR co-chaperone activity of SGT1 to subvert immunity.
title_sort salmonella type iii effector ssph2 specifically exploits the nlr co-chaperone activity of sgt1 to subvert immunity.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/18d8300ef9bc4b3f815eb0cf4287600f
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