Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells

Abstract Lawsonia intracellularis, a Gram-negative obligate intracellular bacterium causing porcine proliferative enteropathy, possesses a type III secretion system (T3SS), yet only a handful of its substrates have been experimentally characterized. In this study, we identify that LI0758 can be secr...

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Main Authors: Yuanxiu Zhong, Yiyun Duan, Fenju Lai, Jinhua Zhang, Yimin Dai
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Veterinary Research
Subjects:
Online Access:https://doi.org/10.1186/s13567-025-01461-8
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author Yuanxiu Zhong
Yiyun Duan
Fenju Lai
Jinhua Zhang
Yimin Dai
author_facet Yuanxiu Zhong
Yiyun Duan
Fenju Lai
Jinhua Zhang
Yimin Dai
author_sort Yuanxiu Zhong
collection DOAJ
description Abstract Lawsonia intracellularis, a Gram-negative obligate intracellular bacterium causing porcine proliferative enteropathy, possesses a type III secretion system (T3SS), yet only a handful of its substrates have been experimentally characterized. In this study, we identify that LI0758 can be secreted by the Yersinia T3SS, which suppresses yeast growth and activates mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway in mammalian cells. Bioinformatics analyses indicate that LI0758 is an ortholog of Rce1, a eukaryotic CAAX protein endoprotease, sharing a similar subcellular localization on the endoplasmic reticulum (ER). While displaying unique activity in the yeast a-factor reporter system, LI0758 restores Ras2 localization in Rce1Δ mutant strains, implying functional similarity. Our findings underscore LI0758’s pivotal role in activating MAPK pathways and suggest its potential to modulate the localization and function of host CAAX proteins. Further investigation holds promise for elucidating novel bacteria-host interaction mechanisms and fostering the development of innovative therapies against proliferative enteritis.
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institution Kabale University
issn 1297-9716
language English
publishDate 2025-02-01
publisher BMC
record_format Article
series Veterinary Research
spelling doaj-art-b8a0ec70ed6d426cb2e347e86376db232025-02-09T12:50:12ZengBMCVeterinary Research1297-97162025-02-0156111610.1186/s13567-025-01461-8Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cellsYuanxiu Zhong0Yiyun Duan1Fenju Lai2Jinhua Zhang3Yimin Dai4School of Biological Science and Engineering, Jiangxi Agricultural UniversitySchool of Biological Science and Engineering, Jiangxi Agricultural UniversitySchool of Biological Science and Engineering, Jiangxi Agricultural UniversitySchool of Animal Science and Technology, Jiangxi Agricultural UniversitySchool of Animal Science and Technology, Jiangxi Agricultural UniversityAbstract Lawsonia intracellularis, a Gram-negative obligate intracellular bacterium causing porcine proliferative enteropathy, possesses a type III secretion system (T3SS), yet only a handful of its substrates have been experimentally characterized. In this study, we identify that LI0758 can be secreted by the Yersinia T3SS, which suppresses yeast growth and activates mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathway in mammalian cells. Bioinformatics analyses indicate that LI0758 is an ortholog of Rce1, a eukaryotic CAAX protein endoprotease, sharing a similar subcellular localization on the endoplasmic reticulum (ER). While displaying unique activity in the yeast a-factor reporter system, LI0758 restores Ras2 localization in Rce1Δ mutant strains, implying functional similarity. Our findings underscore LI0758’s pivotal role in activating MAPK pathways and suggest its potential to modulate the localization and function of host CAAX proteins. Further investigation holds promise for elucidating novel bacteria-host interaction mechanisms and fostering the development of innovative therapies against proliferative enteritis.https://doi.org/10.1186/s13567-025-01461-8L. intracellularistype III secretion systemMAPKNF-κBprenylationRce1
spellingShingle Yuanxiu Zhong
Yiyun Duan
Fenju Lai
Jinhua Zhang
Yimin Dai
Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells
Veterinary Research
L. intracellularis
type III secretion system
MAPK
NF-κB
prenylation
Rce1
title Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells
title_full Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells
title_fullStr Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells
title_full_unstemmed Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells
title_short Lawsonia intracellularis T3SS effector LI0758, an Rce1 ortholog, activates MAPK and NF-κB signaling in mammalian cells
title_sort lawsonia intracellularis t3ss effector li0758 an rce1 ortholog activates mapk and nf κb signaling in mammalian cells
topic L. intracellularis
type III secretion system
MAPK
NF-κB
prenylation
Rce1
url https://doi.org/10.1186/s13567-025-01461-8
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