دورية أكاديمية
A secreted form of chorismate mutase (Rv1885c) in Mycobacterium bovis BCG contributes to pathogenesis by inhibiting mitochondria-mediated apoptotic cell death of macrophages
| العنوان: | A secreted form of chorismate mutase (Rv1885c) in Mycobacterium bovis BCG contributes to pathogenesis by inhibiting mitochondria-mediated apoptotic cell death of macrophages |
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| المؤلفون: | Lee, Mi-Hyun, Kim, Hye Lin, Seo, Hyejun, Jung, Sangkwon, Kim, Bum-Joon |
| بيانات النشر: | BMC |
| سنة النشر: | 2023 |
| المجموعة: | Seoul National University: S-Space |
| مصطلحات موضوعية: | M. bovis BCG, M. tuberculosis, Mycobacterium tuberculosis chorismate mutase (TBCM), Rv1885c, Mitochondrial dysfunction, Intrinsic apoptosis, Macrophages, Deletion mutant, Virulence factor |
| الوصف: | Background Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), and its pathogenicity is associated with its ability to evade the host defense system. The secretory form of the chorismate mutase of M. tuberculosis (TBCM, encoded by Rv1885c) is assumed to play a key role in the pathogenesis of TB; however, the mechanism remains unknown. Methods A tbcm deletion mutant (B∆tbcm) was generated by targeted gene knockout in BCG to investigate the pathogenic role of TBCM in mice or macrophages. We compared the pathogenesis of B∆tbcm and wild-type BCG in vivo by measuring the bacterial clearance rate and the degree of apoptosis. Promotion of the intrinsic apoptotic pathway was evaluated in infected bone marrow-derived macrophages (BMDMs) by measuring apoptotic cell death, loss of mitochondrial membrane potential and translocation of pore-forming proteins. Immunocytochemistry, western blotting and real-time PCR were also performed to assess the related protein expression levels after infection. Furthermore, these findings were validated by complementation of tbcm in BCG. Results Deletion of the tbcm gene in BCG leads to reduced pathogenesis in a mouse model, compared to wild type BCG, by promoting apoptotic cell death and bacterial clearance. Based on these findings, we found that intrinsic apoptosis and mitochondrial impairment were promoted in B∆tbcm-infected BMDMs. B∆tbcm down-regulates the expression of Bcl-2, which leads to mitochondrial outer membrane permeabilization (MOMP), culminating in cytochrome c release from mitochondria. Consistent with this, transcriptome profiling also indicated that B∆tbcm infection is more closely related to altered mitochondrial-related gene expression than wild-type BCG infection, suggesting an inhibitory role of TBCM in mitochondrial dysfunction. Moreover, genetic complementation of B∆tbcm (C∆tbcm) restored its capacity to inhibit mitochondria-mediated apoptotic cell death. Conclusions Our findings demonstrate the contribution of TBCM to bacterial survival, ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1423-0127 |
| العلاقة: | Journal of Biomedical Science, Vol.30(1):95; https://hdl.handle.net/10371/198770Test |
| DOI: | 10.1186/s12929-023-00988-2 |
| الإتاحة: | https://doi.org/10.1186/s12929-023-00988-2Test https://hdl.handle.net/10371/198770Test |
| حقوق: | The Author(s) |
| رقم الانضمام: | edsbas.CB234229 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14230127 |
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| DOI: | 10.1186/s12929-023-00988-2 |