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Mycobacterium tuberculosis PE_PGRS45 (Rv2615c) Promotes Recombinant Mycobacteria Intracellular Survival via Regulation of Innate Immunity, and Inhibition of Cell Apoptosis

  • Microbial Pathogenesis and Host-Microbe Interaction
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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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Data Availability

The datasets generated or analyzed during this study are available from the corresponding author on reasonable request.

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Acknowledgements

This research was supported by the Anhui Provincial Natural Science Foundation (1908085MH252, 2008085QH405), Anhui Province Key Laboratory of Immunology in Chronic Diseases Open Project (KLICD-2022-Z3), Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease Open Project (HX2022Z02), the 512 Talent Cultivation Plan of Bengbu Medical College (by51201309), and the National University Students’ Innovation and Entrepreneurship Training Program (202210367069).

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  1. Tao Xu and Chutong Wang have contributed equally to this work.

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  1. Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Research Center of Laboratory Medicine, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, People’s Republic of China

    Tao Xu, Chutong Wang, Minying Li, Jing Wei, Zixuan He & Zhongqing Qian

  2. Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, First Affiliated Hospital, Bengbu Medical University, Bengbu, 233030, People’s Republic of China

    Xiaojing Wang & Hongtao Wang

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Xu, T., Wang, C., Li, M. et al. Mycobacterium tuberculosis PE_PGRS45 (Rv2615c) Promotes Recombinant Mycobacteria Intracellular Survival via Regulation of Innate Immunity, and Inhibition of Cell Apoptosis. J Microbiol. 62, 49–62 (2024). https://doi.org/10.1007/s12275-023-00101-0

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