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PE_PGRS62 promotes the survival of Mycobacterium smegmatis within macrophages via disrupting ER stress-mediated apoptosis |
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| Authors: | Quanxin Long Xiaohong Xiang Qingqin Yin Shuangjiang Li Wenmin Yang Hang Sun Qi Liu Jianping Xie Wanyan Deng |
| Institution: | 1. Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China
Long and Xiang are co-first authors.;2. School of Pharmacy, Chongqing Medical and Pharmaceutical College, Chongqing, People's Republic of China Long and Xiang are co-first authors.;3. Department of Respiratory Medicine, China National Clinical Research Center for Respiratory Diseases, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, People's Republic of China;4. Department of Physical Examination Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China;5. State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Institute of Modern Biopharmaceuticals, Southwest University, People's Republic of China;6. Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China |
| Abstract: | Mycobacterium tuberculosis, the leading causative agent of tuberculosis, remains one of the most deadly infectious pathogens. PE_PGRS proteins become a new focus as their species specificity in mycobacteria, especially in pathogenic mycobacteria. Despite intensive research, PE_PGRS proteins are still a mysterious aspect of mycobacterial pathogenesis with unknown mechanism. Herein, we focused on a PE_PGRS member from M. tuberculosis, PE_PGRS62, characterized by a surface-exposed protein function in disrupting phagolysosome maturation. Expression of PE_PGRS62 in Mycobacterium smegmatis, a nonpathogenic species naturally deficient in PE_PGRS genes, resulted in enhanced resistance to various in vitro stresses and cellular survival in macrophage. As a consequence, the cytokine profiles of macrophage were disturbed and cell apoptosis were inhibited via decreasing endoplasmic reticulum stress response. |
| Keywords: | apoptosis ER stress response macrophage Mycobacterium tuberculosis PE_PGRS62 tuberculosis |