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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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Abstract
- 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.
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Citations
Citations to this article as recorded by
- 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
- Evolution of the PE_PGRS Proteins of Mycobacteria: Are All Equal or Are Some More Equal than Others?
Review
- MINIREVIEW] Shiga Toxins Expressed by Human Pathogenic Bacteria Induce Immune Responses in Host Cells
- Moo-Seung Lee , Myung Hee Kim , Vernon L. Tesh
- J. Microbiol. 2013;51(6):724-730. Published online December 19, 2013
- DOI: https://doi.org/10.1007/s12275-013-3429-6
- 51 View
- 0 Download
- 21 Crossref
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Abstract
- Shiga toxins are a family of genetically and structurally related toxins that are the primary virulence factors produced by the bacterial pathogens Shigella dysenteriae serotype 1 and certain Escherichia coli strains. The toxins are multifunctional proteins inducing protein biosynthesis inhibition, ribotoxic and ER stress responses, apoptosis, autophagy, and inflammatory cytokine and chemokine production. The regulated induction of inflammatory responses is key to minimizing damage upon injury or pathogen-mediated infections, requiring the concerted activation of multiple signaling pathways to control cytokine/chemokine expression. Activation of host cell signaling cascades is essential for Shiga toxinmediated proinflammatory responses and the contribution of the toxins to virulence. Many studies have been reported defining the inflammatory response to Shiga toxins in vivo and in vitro, including production and secretion of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), macrophage inflammatory protein-1α/β (MIP-1α/β), macrophage chemoattractant monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8), interleukin 6 (IL-6), and Groβ. These cytokines and chemokines may contribute to damage in the colon and development of life threatening conditions such as acute renal failure (hemolytic uremic syndrome) and neurological abnormalities. In this review, we summarize recent findings in Shiga toxin-mediated inflammatory responses by different types of cells in vitro and in animal models. Signaling pathways involved in the inflammatory responses are briefly reviewed.
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Citations
Citations to this article as recorded by- Involvement of aquaporins in Shiga toxin-induced swelling and water transport dysfunction in human renal microvascular endothelial cells
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World Journal of Engineering.2024; 21(6): 1095. CrossRef - Significance of Pulmonary Endothelial Injury and the Role of Cyclooxygenase-2 and Prostanoid Signaling
Rosa Nickl, Sandra Hauser, Jens Pietzsch, Torsten Richter
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Frontiers in Cellular and Infection Microbiology.2020;[Epub] CrossRef - Lactobacillus acidophilus attenuates toxin production by Vibrio cholerae and shigella dysenteriae following intestinal epithelial cells infection
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Moo-Seung Lee, Vernon L. Tesh
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- Involvement of aquaporins in Shiga toxin-induced swelling and water transport dysfunction in human renal microvascular endothelial cells
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