Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection

BackgroundListeria monocytogenes (L. monocytogenes), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of L. monocytogenes-host in...

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Main Authors: Lei Xu, Yonglin Zhou, Jingwen Xu, Xiangzhu Xu, Gejin Lu, Qianghua Lv, Lijuan Wei, Xuming Deng, Xue Shen, Haihua Feng, Jianfeng Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-10-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.977051/full
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author Lei Xu
Lei Xu
Yonglin Zhou
Yonglin Zhou
Jingwen Xu
Xiangzhu Xu
Gejin Lu
Gejin Lu
Qianghua Lv
Lijuan Wei
Xuming Deng
Xue Shen
Haihua Feng
Haihua Feng
Jianfeng Wang
Jianfeng Wang
author_facet Lei Xu
Lei Xu
Yonglin Zhou
Yonglin Zhou
Jingwen Xu
Xiangzhu Xu
Gejin Lu
Gejin Lu
Qianghua Lv
Lijuan Wei
Xuming Deng
Xue Shen
Haihua Feng
Haihua Feng
Jianfeng Wang
Jianfeng Wang
author_sort Lei Xu
collection DOAJ
description BackgroundListeria monocytogenes (L. monocytogenes), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of L. monocytogenes-host interactions.MethodsHemolysis assay was employed to screen a potential LLO inhibitor and the underlying mechanisms were investigated using molecular dynamics (MD) simulation and oligomerization assay. The effects of candidates on immune response were examined by qRT-PCR and immunoblotting analysis. Histological analysis, ELISA assay and biochemistry detection were conducted to assess in vivo efficacy of candidates.ResultsIn the present study, natural terpenoid atractylodin was characterized as an alternative drug candidate for the treatment of L. monocytogenes by the regulation of LLO function and host Nrf2/NLRP3 signaling pathway. Notably, in vivo infection model by L. monocytogenes also highlighted that atractylodin treatment provided effective therapeutic benefits, as evidenced by decreased bacterial burden and diminished inflammation. Congruently, the survival rate of L. monocytogenes-infection mice increased significantly from 10.0% to 40.0% by atractylodin treatment.ConclusionCollectively, our study showed for the first time that atractylodin has tremendous potential to attenuate L. monocytogenes pathogenicity by blocking LLO pore formation and mediating the suppression of inflammation and oxidative stress, providing a promising therapeutic strategy and broadening the applications of atractylodin against L. monocytogenes infection.
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spelling doaj.art-922f315258cc429589e72115c506dff42022-12-22T04:34:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.977051977051Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infectionLei Xu0Lei Xu1Yonglin Zhou2Yonglin Zhou3Jingwen Xu4Xiangzhu Xu5Gejin Lu6Gejin Lu7Qianghua Lv8Lijuan Wei9Xuming Deng10Xue Shen11Haihua Feng12Haihua Feng13Jianfeng Wang14Jianfeng Wang15Department of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaChangchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaHebei Veterinary Medicine Technology Innovation Center, Shijiazhuang, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Food Science, College of Food Science and Engineering, Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaDepartment of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, ChinaState Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, ChinaBackgroundListeria monocytogenes (L. monocytogenes), as a pandemic foodborne pathogen, severely threatens food security and public health care worldwide, which evolves multiple bacterial virulence factors (such as listeriolysin O, LLO) for manipulating the immune response of L. monocytogenes-host interactions.MethodsHemolysis assay was employed to screen a potential LLO inhibitor and the underlying mechanisms were investigated using molecular dynamics (MD) simulation and oligomerization assay. The effects of candidates on immune response were examined by qRT-PCR and immunoblotting analysis. Histological analysis, ELISA assay and biochemistry detection were conducted to assess in vivo efficacy of candidates.ResultsIn the present study, natural terpenoid atractylodin was characterized as an alternative drug candidate for the treatment of L. monocytogenes by the regulation of LLO function and host Nrf2/NLRP3 signaling pathway. Notably, in vivo infection model by L. monocytogenes also highlighted that atractylodin treatment provided effective therapeutic benefits, as evidenced by decreased bacterial burden and diminished inflammation. Congruently, the survival rate of L. monocytogenes-infection mice increased significantly from 10.0% to 40.0% by atractylodin treatment.ConclusionCollectively, our study showed for the first time that atractylodin has tremendous potential to attenuate L. monocytogenes pathogenicity by blocking LLO pore formation and mediating the suppression of inflammation and oxidative stress, providing a promising therapeutic strategy and broadening the applications of atractylodin against L. monocytogenes infection.https://www.frontiersin.org/articles/10.3389/fimmu.2022.977051/fullatractylodinListeria monocytogeneslisteriolysin ONLRP3Nrf2
spellingShingle Lei Xu
Lei Xu
Yonglin Zhou
Yonglin Zhou
Jingwen Xu
Xiangzhu Xu
Gejin Lu
Gejin Lu
Qianghua Lv
Lijuan Wei
Xuming Deng
Xue Shen
Haihua Feng
Haihua Feng
Jianfeng Wang
Jianfeng Wang
Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection
Frontiers in Immunology
atractylodin
Listeria monocytogenes
listeriolysin O
NLRP3
Nrf2
title Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection
title_full Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection
title_fullStr Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection
title_full_unstemmed Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection
title_short Anti-inflammatory, antioxidant and anti-virulence roles of atractylodin in attenuating Listeria monocytogenes infection
title_sort anti inflammatory antioxidant and anti virulence roles of atractylodin in attenuating listeria monocytogenes infection
topic atractylodin
Listeria monocytogenes
listeriolysin O
NLRP3
Nrf2
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.977051/full
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