Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB

Salmonella Infantis has emerged as a major clinical pathogen causing gastroenteritis worldwide in recent years. As an intracellular pathogen, Salmonella has evolved to manipulate and benefit from the cell death signaling pathway. In this study, we discovered that S. Infantis inhibited apoptosis of i...

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Autores principales: Bing-Xin Chu, Ya-Nan Li, Ning- Liu, Lan-Xin Yuan, Shi-Yan Chen, Yao-Hong Zhu, Jiu-Feng Wang
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/80c0daeffa954c25869b59c3827ee5d4
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spelling oai:doaj.org-article:80c0daeffa954c25869b59c3827ee5d42021-11-05T08:58:15ZSalmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB1664-322410.3389/fimmu.2021.757909https://doaj.org/article/80c0daeffa954c25869b59c3827ee5d42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.757909/fullhttps://doaj.org/toc/1664-3224Salmonella Infantis has emerged as a major clinical pathogen causing gastroenteritis worldwide in recent years. As an intracellular pathogen, Salmonella has evolved to manipulate and benefit from the cell death signaling pathway. In this study, we discovered that S. Infantis inhibited apoptosis of infected Caco-2 cells by phosphorylating Akt. Notably, Akt phosphorylation was observed in a discontinuous manner: immediately 0.5 h after the invasion, then before peak cytosolic replication. Single-cell analysis revealed that the second phase was only induced by cytosolic hyper-replicating bacteria at 3–4 hpi. Next, Akt-mediated apoptosis inhibition was found to be initiated by Salmonella SopB. Furthermore, Akt phosphorylation increased mitochondrial localization of Bcl-2 to prevent Bax oligomerization on the mitochondrial membrane, maintaining the mitochondrial network homeostasis to resist apoptosis. In addition, S. Infantis induced pyroptosis, as evidenced by increased caspase-1 (p10) and GSDMS-N levels. In contrast, cells infected with the ΔSopB strain displayed faster but less severe pyroptosis and had less bacterial load. The results indicated that S. Infantis SopB–mediated Akt phosphorylation delayed pyroptosis, but aggravated its severity. The wild-type strain also caused more severe diarrhea and intestinal inflammatory damage than the ΔSopB strain in mice. These findings revealed that S. Infantis delayed the cells’ death by intermittent activation of Akt, allowing sufficient time for replication, thereby causing more severe inflammation.Bing-Xin ChuYa-Nan LiNing- LiuLan-Xin YuanShi-Yan ChenYao-Hong ZhuJiu-Feng WangFrontiers Media S.A.articleSalmonella InfantisAktSopBapoptosispyroptosisinflammationImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Salmonella Infantis
Akt
SopB
apoptosis
pyroptosis
inflammation
Immunologic diseases. Allergy
RC581-607
spellingShingle Salmonella Infantis
Akt
SopB
apoptosis
pyroptosis
inflammation
Immunologic diseases. Allergy
RC581-607
Bing-Xin Chu
Ya-Nan Li
Ning- Liu
Lan-Xin Yuan
Shi-Yan Chen
Yao-Hong Zhu
Jiu-Feng Wang
Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
description Salmonella Infantis has emerged as a major clinical pathogen causing gastroenteritis worldwide in recent years. As an intracellular pathogen, Salmonella has evolved to manipulate and benefit from the cell death signaling pathway. In this study, we discovered that S. Infantis inhibited apoptosis of infected Caco-2 cells by phosphorylating Akt. Notably, Akt phosphorylation was observed in a discontinuous manner: immediately 0.5 h after the invasion, then before peak cytosolic replication. Single-cell analysis revealed that the second phase was only induced by cytosolic hyper-replicating bacteria at 3–4 hpi. Next, Akt-mediated apoptosis inhibition was found to be initiated by Salmonella SopB. Furthermore, Akt phosphorylation increased mitochondrial localization of Bcl-2 to prevent Bax oligomerization on the mitochondrial membrane, maintaining the mitochondrial network homeostasis to resist apoptosis. In addition, S. Infantis induced pyroptosis, as evidenced by increased caspase-1 (p10) and GSDMS-N levels. In contrast, cells infected with the ΔSopB strain displayed faster but less severe pyroptosis and had less bacterial load. The results indicated that S. Infantis SopB–mediated Akt phosphorylation delayed pyroptosis, but aggravated its severity. The wild-type strain also caused more severe diarrhea and intestinal inflammatory damage than the ΔSopB strain in mice. These findings revealed that S. Infantis delayed the cells’ death by intermittent activation of Akt, allowing sufficient time for replication, thereby causing more severe inflammation.
format article
author Bing-Xin Chu
Ya-Nan Li
Ning- Liu
Lan-Xin Yuan
Shi-Yan Chen
Yao-Hong Zhu
Jiu-Feng Wang
author_facet Bing-Xin Chu
Ya-Nan Li
Ning- Liu
Lan-Xin Yuan
Shi-Yan Chen
Yao-Hong Zhu
Jiu-Feng Wang
author_sort Bing-Xin Chu
title Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
title_short Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
title_full Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
title_fullStr Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
title_full_unstemmed Salmonella Infantis Delays the Death of Infected Epithelial Cells to Aggravate Bacterial Load by Intermittent Phosphorylation of Akt With SopB
title_sort salmonella infantis delays the death of infected epithelial cells to aggravate bacterial load by intermittent phosphorylation of akt with sopb
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/80c0daeffa954c25869b59c3827ee5d4
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