Ali Md Kaisar, Nzungize Lambert, Abbas Khushnood, Eckzechel Nzaou Stech Anomene, Abo-Kadoum M A, Moure Ulrich Aymard Ekomi, Asaad Mohammed, Alam Aftab, Xu Junqi, Xie Jianping
Institute of Modern Biopharmaceuticals, 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 Science, Southwest University, Beibei, Chongqing 400715, China.
College of Animal Science and Technology, Southwest University, Beibei, Chongqing 400715, China.
Pathogens. 2021 Feb 1;10(2):143. doi: 10.3390/pathogens10020143.
The () genome encodes a large number of hypothetical proteins, which need to investigate their role in physiology, virulence, pathogenesis, and host interaction. To explore the role of hypothetical protein Rv0580c, we constructed the recombinant () strain, which expressed the Rv0580c protein heterologously. We observed that Rv0580c expressing strain (Ms_Rv0580c) altered the colony morphology and increased the cell wall permeability, leading to this recombinant strain becoming susceptible to acidic stress, oxidative stress, cell wall-perturbing stress, and multiple antibiotics. The intracellular survival of Ms_Rv0580c was reduced in THP-1 macrophages. Ms_Rv0580c up-regulated the IFN-γ expression via NF-κB and JNK signaling, and down-regulated IL-10 expression via NF-κB signaling in THP-1 macrophages as compared to control. Moreover, Ms_Rv0580c up-regulated the expression of and ER stress marker genes via the NF-κB/JNK axis and JNK/p38 axis, respectively, and boosted the mitochondria-independent apoptosis in macrophages, which might be lead to eliminate the intracellular bacilli. This study explores the crucial role of Rv0580c protein in the physiology and novel host-pathogen interactions of mycobacteria.
（）基因组编码大量假定蛋白，需要研究它们在生理学、毒力、发病机制及与宿主相互作用中的作用。为探究假定蛋白Rv0580c的作用，我们构建了重组（）菌株，该菌株可异源表达Rv0580c蛋白。我们观察到表达Rv0580c的菌株（Ms_Rv0580c）改变了菌落形态并增加了细胞壁通透性，导致该重组菌株对酸性应激、氧化应激、细胞壁干扰应激及多种抗生素敏感。Ms_Rv0580c在THP-1巨噬细胞中的胞内存活能力降低。与对照相比，Ms_Rv0580c在THP-1巨噬细胞中通过NF-κB和JNK信号上调IFN-γ表达，并通过NF-κB信号下调IL-10表达。此外，Ms_Rv0580c分别通过NF-κB/JNK轴和JNK/p38轴上调（）和内质网应激标记基因的表达，并促进巨噬细胞中不依赖线粒体的凋亡，这可能导致细胞内杆菌被清除。本研究探讨了Rv0580c蛋白在分枝杆菌生理学及新型宿主-病原体相互作用中的关键作用。
