<i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell Ferroptosis
<i>Vibrio alginolyticus</i> is a Gram-negative pathogen of both marine animals and humans, resulting in significant losses for the aquaculture industry. Emerging evidence indicates that <i>V. alginolyticus</i> manipulates cell death for its pathogenicity, but the underlying m...
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2024-11-01
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| author | Weijie Zhang Chao Huang Zhihang Chen Dawei Song Yujia Zhang Shuai Yang Na Wang Jichang Jian Huanying Pang |
| author_facet | Weijie Zhang Chao Huang Zhihang Chen Dawei Song Yujia Zhang Shuai Yang Na Wang Jichang Jian Huanying Pang |
| author_sort | Weijie Zhang |
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| description | <i>Vibrio alginolyticus</i> is a Gram-negative pathogen of both marine animals and humans, resulting in significant losses for the aquaculture industry. Emerging evidence indicates that <i>V. alginolyticus</i> manipulates cell death for its pathogenicity, but the underlying molecular mechanisms remain unclear. Here, a gene designated <i>vopS</i> in <i>V. alginolyticus</i> HY9901 was identified, which was predicted to encode the T3SS effector protein. To determine whether VopS contributes to the pathogenesis of <i>V. alginolyticus</i>, the Δ<i>vopS</i> mutant strain was constructed and phenotypically characterized. The deletion of VopS not only reduced the ability to secrete extracellular proteases and virulence but also affected the expression of the T3SS genes. Furthermore, VopS was cytotoxic and induced apoptosis, as confirmed by elevated LDH and the activation of caspase-3. Metabolomic analysis revealed considerable metabolomic disruptions upon <i>V. alginolyticus</i> infection. The VopS effector induced host cell ferroptosis by promoting the synthesis of adrenic acid, depleting cellular glutathione, and subsequently increasing the accumulation of ferrous (Fe<sup>2+</sup>). Taken together, our findings provide that the VopS effector is an essential virulence factor of <i>V. alginolyticus</i>, which can lead to ferroptosis. |
| format | Article |
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| institution | OA Journals |
| issn | 2076-2615 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-4c1616b8ca3b4fb2b10657afea26747c2025-08-20T01:53:52ZengMDPI AGAnimals2076-26152024-11-011422325010.3390/ani14223250<i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell FerroptosisWeijie Zhang0Chao Huang1Zhihang Chen2Dawei Song3Yujia Zhang4Shuai Yang5Na Wang6Jichang Jian7Huanying Pang8Fisheries College, Guangdong Ocean University, Zhanjiang 524025, ChinaFisheries College, Guangdong Ocean University, Zhanjiang 524025, ChinaFisheries College, Guangdong Ocean University, Zhanjiang 524025, ChinaFisheries College, Guangdong Ocean University, Zhanjiang 524025, ChinaFisheries College, Guangdong Ocean University, Zhanjiang 524025, ChinaFisheries College, Guangdong Ocean University, Zhanjiang 524025, ChinaChinese Academy of Inspection and Quarantine, Beijing 100176, ChinaFisheries College, Guangdong Ocean University, Zhanjiang 524025, ChinaFisheries College, Guangdong Ocean University, Zhanjiang 524025, China<i>Vibrio alginolyticus</i> is a Gram-negative pathogen of both marine animals and humans, resulting in significant losses for the aquaculture industry. Emerging evidence indicates that <i>V. alginolyticus</i> manipulates cell death for its pathogenicity, but the underlying molecular mechanisms remain unclear. Here, a gene designated <i>vopS</i> in <i>V. alginolyticus</i> HY9901 was identified, which was predicted to encode the T3SS effector protein. To determine whether VopS contributes to the pathogenesis of <i>V. alginolyticus</i>, the Δ<i>vopS</i> mutant strain was constructed and phenotypically characterized. The deletion of VopS not only reduced the ability to secrete extracellular proteases and virulence but also affected the expression of the T3SS genes. Furthermore, VopS was cytotoxic and induced apoptosis, as confirmed by elevated LDH and the activation of caspase-3. Metabolomic analysis revealed considerable metabolomic disruptions upon <i>V. alginolyticus</i> infection. The VopS effector induced host cell ferroptosis by promoting the synthesis of adrenic acid, depleting cellular glutathione, and subsequently increasing the accumulation of ferrous (Fe<sup>2+</sup>). Taken together, our findings provide that the VopS effector is an essential virulence factor of <i>V. alginolyticus</i>, which can lead to ferroptosis.https://www.mdpi.com/2076-2615/14/22/3250<i>Vibrio alginolyticus</i>T3SS<i>vopS</i>metabolomicsferroptosis |
| spellingShingle | Weijie Zhang Chao Huang Zhihang Chen Dawei Song Yujia Zhang Shuai Yang Na Wang Jichang Jian Huanying Pang <i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell Ferroptosis Animals <i>Vibrio alginolyticus</i> T3SS <i>vopS</i> metabolomics ferroptosis |
| title | <i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell Ferroptosis |
| title_full | <i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell Ferroptosis |
| title_fullStr | <i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell Ferroptosis |
| title_full_unstemmed | <i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell Ferroptosis |
| title_short | <i>Vibrio alginolyticus</i> Reprograms CIK Cell Metabolism via T3SS Effector VopS to Promote Host Cell Ferroptosis |
| title_sort | i vibrio alginolyticus i reprograms cik cell metabolism via t3ss effector vops to promote host cell ferroptosis |
| topic | <i>Vibrio alginolyticus</i> T3SS <i>vopS</i> metabolomics ferroptosis |
| url | https://www.mdpi.com/2076-2615/14/22/3250 |
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