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Mycobacterium tuberculosis PE_PGRS45 (Rv2615c) Promotes Recombinant Mycobacteria Intracellular Survival via Regulation of Innate Immunity, and Inhibition of Cell Apoptosis
Tao Xu , Chutong Wang , Minying Li , Jing Wei , Zixuan He , Zhongqing Qian , Xiaojing Wang , Hongtao Wang
J. Microbiol. 2024;62(1):49-62.   Published online February 9, 2024
DOI: https://doi.org/10.1007/s12275-023-00101-0
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AbstractAbstract
Tuberculosis (TB), a bacterial infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), is a significant global public health problem. Mycobacterium tuberculosis expresses a unique family of PE_PGRS proteins that have been implicated in pathogenesis. Despite numerous studies, the functions of most PE_PGRS proteins in the pathogenesis of mycobacterium infections remain unclear. PE_PGRS45 (Rv2615c) is only found in pathogenic mycobacteria. In this study, we successfully constructed a recombinant Mycobacterium smegmatis (M. smegmatis) strain which heterologously expresses the PE_PGRS45 protein. We found that overexpression of this cell wall-associated protein enhanced bacterial viability under stress in vitro and cell survival in macrophages. MS_PE_PGRS45 decreased the secretion of pro-inflammatory cytokines such as IL-1β, IL-6, IL-12p40, and TNF-α. We also found that MS_PE_PGRS45 increased the expression of the anti-inflammatory cytokine IL-10 and altered macrophage-mediated immune responses. Furthermore, PE_PGRS45 enhanced the survival rate of M. smegmatis in macrophages by inhibiting cell apoptosis. Collectively, our findings show that PE_PGRS45 is a virulent factor actively involved in the interaction with the host macrophage.

Citations

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  • Evolution of the PE_PGRS Proteins of Mycobacteria: Are All Equal or Are Some More Equal than Others?
    Bei Chen, Belmin Bajramović, Bastienne Vriesendorp, Herman Pieter Spaink
    Biology.2025; 14(3): 247.     CrossRef
  • Recent advances in research on Mycobacterium tuberculosis virulence factors and their role in pathogenesis
    Ming-Rui Sun, Jia-Yin Xing, Xiao-Tian Li, Ren Fang, Yang Zhang, Zhao-Li Li, Ning-Ning Song
    Journal of Microbiology, Immunology and Infection.2025;[Epub]     CrossRef
  • Rv2741 Promotes Mycobacterium Survival by Modulating Macrophage Function via the IL-1α-MAPK Axis
    Xintong He, Yonglin He, Xichuan Deng, Nan Lu, Anlong Li, Sijia Gao, Shiyan He, Yuran Wang, Nanzhe Fu, Zijie Wang, Yuxin Nie, Lei Xu
    ACS Infectious Diseases.2025; 11(3): 676.     CrossRef

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