| Title | Mycobacterium tuberculosis PE_PGRS45 (Rv2615c) Promotes Recombinant Mycobacteria Intracellular Survival via Regulation of Innate Immunity, and Inhibition of Cell Apoptosis |
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| Author | Tao Xu1†, Chutong Wang1†, Minying Li1, Jing Wei1, Zixuan He1, Zhongqing Qian1, Xiaojing Wang2, and Hongtao Wang2* |
| Address | 1Anhui 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, 2Anhui 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 |
| Bibliography | Journal of Microbiology, 62(1),49-62, 2024, |
| DOI | 10.1007/s12275-023-00101-0 |
| Key Words | Mycobacterium tuberculosis · PE_PGRS45 · Cytokines · Apoptosis |
| 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. |