Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis
Escherichia coli (E. coli), a major foodborne pathogen, poses significant risks to public health by causing gastrointestinal diseases. Among its virulence factors, Yersiniabactin (Ybt), a siderophore, plays a crucial role in iron acquisition and enhancing intestinal colonization. Despite previous st...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1542801/full |
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| author | Hao Wang Bingxun Chen Peng Xiao Dongmei Han Bin Gao Yulin Yan Ru Zhao Tianling Pan Jingsong Zhang Meng Zhou Longbao Lv Hong Gao |
| author_facet | Hao Wang Bingxun Chen Peng Xiao Dongmei Han Bin Gao Yulin Yan Ru Zhao Tianling Pan Jingsong Zhang Meng Zhou Longbao Lv Hong Gao |
| author_sort | Hao Wang |
| collection | DOAJ |
| description | Escherichia coli (E. coli), a major foodborne pathogen, poses significant risks to public health by causing gastrointestinal diseases. Among its virulence factors, Yersiniabactin (Ybt), a siderophore, plays a crucial role in iron acquisition and enhancing intestinal colonization. Despite previous studies highlighting E. coli-Ybt’s involvement in inflammation, its exact mechanisms remain unclear. This study investigates how Ybt contributes to intestinal inflammation through ferroptosis, using both in vitro and in vivo models. Our findings demonstrate that Ybt promotes oxidative stress, lipid peroxidation, inflammation, and iron accumulation in intestinal epithelial cells, leading to ferroptosis. Mechanistically, Ybt suppresses the Keap1/Nrf2 pathway, amplifying reactive oxygen species (ROS) and activating the TNF/NF-κB pathway, which drives inflammation. Moreover, Ybt induces lipid peroxidation via the arachidonic acid pathway, producing 6-trans-leukotriene B4 (6-transLTB4), which exacerbates inflammation and ferroptosis. Exogenous 6-transLTB4 further intensifies this cascade. Additionally, Ybt disrupts iron efflux by suppressing FPN1 expression, causing excessive intracellular iron accumulation. Using tree shrews as an in vivo model, we confirm that Ybt-induced ferroptosis significantly aggravates intestinal inflammation. These findings underscore the pathogenic role of Ybt in E. coli-induced intestinal injury and highlight ferroptosis as a novel mechanism contributing to gut health disruption. This study provides new insights into the molecular pathways of E. coli infection, with implications for therapeutic strategies targeting ferroptosis in intestinal diseases. |
| format | Article |
| id | doaj-art-19fd96c7e48c46a585c04bd31f2949fc |
| institution | OA Journals |
| issn | 1664-302X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj-art-19fd96c7e48c46a585c04bd31f2949fc2025-08-20T02:13:07ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-02-011610.3389/fmicb.2025.15428011542801Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosisHao Wang0Bingxun Chen1Peng Xiao2Dongmei Han3Bin Gao4Yulin Yan5Ru Zhao6Tianling Pan7Jingsong Zhang8Meng Zhou9Longbao Lv10Hong Gao11College of Food Science and Technology, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Food Science and Technology, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaCollege of Food Science and Technology, Yunnan Agricultural University, Kunming, ChinaNational Resource Center for Non-Human Primates, National Research Facility for Phenotypic and Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, ChinaCollege of Veterinary Medicine, Yunnan Agricultural University, Kunming, ChinaEscherichia coli (E. coli), a major foodborne pathogen, poses significant risks to public health by causing gastrointestinal diseases. Among its virulence factors, Yersiniabactin (Ybt), a siderophore, plays a crucial role in iron acquisition and enhancing intestinal colonization. Despite previous studies highlighting E. coli-Ybt’s involvement in inflammation, its exact mechanisms remain unclear. This study investigates how Ybt contributes to intestinal inflammation through ferroptosis, using both in vitro and in vivo models. Our findings demonstrate that Ybt promotes oxidative stress, lipid peroxidation, inflammation, and iron accumulation in intestinal epithelial cells, leading to ferroptosis. Mechanistically, Ybt suppresses the Keap1/Nrf2 pathway, amplifying reactive oxygen species (ROS) and activating the TNF/NF-κB pathway, which drives inflammation. Moreover, Ybt induces lipid peroxidation via the arachidonic acid pathway, producing 6-trans-leukotriene B4 (6-transLTB4), which exacerbates inflammation and ferroptosis. Exogenous 6-transLTB4 further intensifies this cascade. Additionally, Ybt disrupts iron efflux by suppressing FPN1 expression, causing excessive intracellular iron accumulation. Using tree shrews as an in vivo model, we confirm that Ybt-induced ferroptosis significantly aggravates intestinal inflammation. These findings underscore the pathogenic role of Ybt in E. coli-induced intestinal injury and highlight ferroptosis as a novel mechanism contributing to gut health disruption. This study provides new insights into the molecular pathways of E. coli infection, with implications for therapeutic strategies targeting ferroptosis in intestinal diseases.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1542801/fullEscherichia coliyersiniabactinlipid peroxidationferroptosisintestinal inflammation |
| spellingShingle | Hao Wang Bingxun Chen Peng Xiao Dongmei Han Bin Gao Yulin Yan Ru Zhao Tianling Pan Jingsong Zhang Meng Zhou Longbao Lv Hong Gao Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis Frontiers in Microbiology Escherichia coli yersiniabactin lipid peroxidation ferroptosis intestinal inflammation |
| title | Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis |
| title_full | Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis |
| title_fullStr | Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis |
| title_full_unstemmed | Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis |
| title_short | Yersiniabactin produced by Escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis |
| title_sort | yersiniabactin produced by escherichia coli promotes intestinal inflammation through lipid peroxidation and ferroptosis |
| topic | Escherichia coli yersiniabactin lipid peroxidation ferroptosis intestinal inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2025.1542801/full |
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