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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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) |
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Salmonella Infantis Akt SopB apoptosis pyroptosis inflammation Immunologic diseases. Allergy RC581-607 |
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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 |
work_keys_str_mv |
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