Full article
- Bak and Bax are crucial for Gbp2-mediated pyroptosis during Vibrio and Salmonella infections
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Yongyang Luo, Jeehyeon Bae
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J. Microbiol. 2025;63(9):e2508004. Published online September 30, 2025
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DOI: https://doi.org/10.71150/jm.2508004
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Abstract
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Supplementary Material
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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
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Seulki Lee , Hwan Hee Lee , Jisung Kim , Joohee Jung , Aree Moon , Choon-Sik Jeong , Hyojeung Kang , Hyosun Cho
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J. Microbiol. 2015;53(7):468-474. Published online June 27, 2015
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DOI: https://doi.org/10.1007/s12275-015-5198-x
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Abstract
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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.
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