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Bak and Bax are crucial for Gbp2-mediated pyroptosis during Vibrio and Salmonella infections
Yongyang Luo, Jeehyeon Bae
J. Microbiol. 2025;63(9):e2508004.   Published online September 30, 2025
DOI: https://doi.org/10.71150/jm.2508004
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AbstractAbstract PDFSupplementary Material

Pyroptosis a lytic form of programmed cell death, is a crucial host defense mechanism against bacterial pathogens. While caspase-mediated pathways are central to pyroptosis, the involvement of apoptotic regulators such as Bak, Bax, and MCL-1 in bacterial infection-induced pyroptosis remains unclear. Here, we investigated how these BCL-2 family proteins modulate pyroptosis induced by Vibrio vulnificus and Salmonella enterica serovar Typhimurium in murine cells. In mouse embryonic fibroblasts (MEFs), both pathogens strongly induced Gbp2 expression and activated caspase‑11, whereas activation of caspase‑1 occurred only in macrophages, indicating engagement of both non-canonical and canonical pyroptosis pathways. Importantly, Bak-/- and Bax-/- MEFs exhibited significantly reduced Gbp2 upregulation and caspase-11 activation-an effect most pronounced in Bak-deficient cells leading to attenuated pyroptotic cell death. These data suggest that pro-apoptotic proteins, Bak and Bax, act as positive regulators that amplify the Gbp2-caspase-11 axis. Conversely, overexpression of the anti-apoptotic protein MCL‑1 had no significant impact on Gbp2 expression, caspase activation, membrane integrity, or LDH release, indicating that pyroptosis proceeds independently of MCL‑1 regulation. Collectively, our findings uncover a novel role for Bak and Bax in promoting Gbp2-driven pyroptosis during Gram-negative bacterial infections, while MCL‑1 does not impede this process. This work expands our understanding of the crosstalk between apoptotic and pyroptotic pathways in innate immune responses.

Research Support, Non-U.S. Gov't
Anti-tumor effect of Cordyceps militaris in HCV-infected human hepatocarcinoma 7.5 cells
Seulki Lee , Hwan Hee Lee , Jisung Kim , Joohee Jung , Aree Moon , Choon-Sik Jeong , Hyojeung Kang , Hyosun Cho
J. Microbiol. 2015;53(7):468-474.   Published online June 27, 2015
DOI: https://doi.org/10.1007/s12275-015-5198-x
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  • 9 Crossref
AbstractAbstract
Cordyceps extract has been reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris on hepatitis C virus-infected human hepatocarcinoma 7.5 cells (J6/JFH1-huh 7.5 cells). The huh7.5 cells with or without HCV infection were treated with various concentrations of ethanol extract of Cordyceps militaris (CME) for 48 h and the cytotoxicity was measured by CCK-8 assay. Both J6/JFH1- huh7.5 cells and huh7.5 cells were highly susceptible to CME. To examine the molecular mechanisms of the inhibitory effect on huh7.5 cells, the effect of CME on cell apoptosis was measured using flow cytometry and the expressions of p53, Bim, Bax, PARP, (cleaved) caspase-9, and (cleaved) caspase- 3 in huh 7.5 cells were detected by western blot assays. CME significantly increased early apoptosis and up-regulated the expression of Bim, Bax, cleaved PARP, cleaved caspase 9 and cleaved caspase-3. We also found the decrease of HCV Core or NS3 protein by CME in HCV-infected huh 7.5 cells.

Citations

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  • Visualized Nucleic Acid Hybridization Lateral Flow Strip Integrating with Microneedle for the Point-of-Care Authentication of Ophiocordyceps sinensis
    Haibin Liu, Xinyue Wang, Hang Tian, Yi Yuan, Jing Wang, Yani Cheng, Linyao Sun, Hongshuo Chen, Xiaoming Song
    International Journal of Molecular Sciences.2024; 25(24): 13599.     CrossRef
  • Novel formulation development from Ophiocordyceps sinensis (Berk.) for management of high-altitude maladies
    Rakhee, Jigni Mishra, Renu Bala Yadav, D. K. Meena, Rajesh Arora, R. K. Sharma, Kshipra Misra
    3 Biotech.2021;[Epub]     CrossRef
  • A new nucleoside and two new pyrrole alkaloid derivatives from Cordyceps militaris
    Yafu Xue, Leilei Wu, Yulian Ding, Xinming Cui, Zhuzhen Han, Hong Xu
    Natural Product Research.2020; 34(3): 341.     CrossRef
  • Antitumor and Anti-Invasive Effect of Apigenin on Human Breast Carcinoma through Suppression of IL-6 Expression
    Hwan Hee Lee, Joohee Jung, Aree Moon, Hyojeung Kang, Hyosun Cho
    International Journal of Molecular Sciences.2019; 20(13): 3143.     CrossRef
  • Cytokine-Modulated Natural Killer Cells Differentially Regulate the Activity of the Hepatitis C Virus
    Yoo Cho, Hwan Lee, Hyojeung Kang, Hyosun Cho
    International Journal of Molecular Sciences.2018; 19(9): 2771.     CrossRef
  • The genus Cordyceps : An extensive review of its traditional uses, phytochemistry and pharmacology
    Opeyemi Joshua Olatunji, Jian Tang, Adesola Tola, Florence Auberon, Omolara Oluwaniyi, Zhen Ouyang
    Fitoterapia.2018; 129: 293.     CrossRef
  • Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis
    Jingbo Wang, Rui Liu, Baoxiu Liu, Yan Yang, Jun Xie, Naishuo Zhu
    Scientific Reports.2017;[Epub]     CrossRef
  • Anti-Cancer Effect of Quercetin in Xenograft Models with EBV-Associated Human Gastric Carcinoma
    Hwan Lee, Seulki Lee, Yu Shin, Miyeon Cho, Hyojeung Kang, Hyosun Cho
    Molecules.2016; 21(10): 1286.     CrossRef
  • Anti-tumor effect of Inonotus obliquus in xenograft animals with EBV+human gastric carcinoma
    Seulki Lee, Hyosun Cho
    The Korean Journal of Microbiology.2016; 52(4): 482.     CrossRef

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