1. Mycobacterium tuberculosis PPE10 (Rv0442c) alters host cell apoptosis and cytokine profile via linear ubiquitin chain assembly complex HOIP-NF-κB signaling axis
- Author
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M.A. Abo-kadoum, Kaisar Ali, Hao Wang, Nzungize Lambert, Stech A.E. Nazou, Moure Uae, Jianping Xie, Mohammed Asaad, Zhen Gong, and Zhongmei Kuang
- Subjects
0301 basic medicine ,THP-1 Cells ,Ubiquitin-Protein Ligases ,Immunology ,Apoptosis ,Mycobacterium tuberculosis ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Ubiquitin ,medicine ,Humans ,Immunology and Allergy ,Macrophage ,Gene ,Caspase ,Pharmacology ,biology ,Chemistry ,NF-kappa B ,NF-κB ,Hydrogen-Ion Concentration ,biology.organism_classification ,Cell biology ,030104 developmental biology ,Mechanism of action ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,biology.protein ,Cytokines ,medicine.symptom ,Signal Transduction - Abstract
Tuberculosis caused by Mycobacterium tuberculosis infection remains one of the top ten causes of deaths worldwide. M. tuberculosis genome devoted 10% capacity for highly repeated PE/PPE genes family. To explore the role of PPE10 in host-pathogen interaction, PPE10 encoding gene Rv0442c was heterologously expressed in the nonpathogenic M. smegmatis strain. PPE10 altered the bacterial cell surface properties, colony morphology, and biofilm formation. Ms_PPE10 showed more resistance to stress conditions such as diamide, and low pH, as well as higher survival within the macrophage. Moreover, the host's cell apoptosis was regulated via decreased expression of caspases, IL-1, IL-6, and TNF-α through the Linear Ubiquitin Chain Assembly Complex (LUBAC) HOIP-NF-κB signaling axis. The study revealed novel insights into the mechanism of action of the PPE family.
- Published
- 2021
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