Rv2037c, a stress induced conserved hypothetical protein of Mycobacterium tuberculosis, is a phospholipase: Role in cell wall modulation and intracellular survival
Rv2037c, a stress induced conserved hypothetical protein of Mycobacterium tuberculosis, is a phospholipase: Role in cell wall modulation and intracellular survival
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DOI：
10.1016/j.ijbiomac.2020.03.037
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发表时间：
2020-06-15
影响因子：
8.2
通讯作者：
Kaur, Jagdeep
中科院分区：
文献类型：
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作者：
Kumari, Bandana;Saini, Varinder;Kaur, Jagdeep
结核分枝杆菌的基因组编码了几种需要表征的假设蛋白质。 Rv2037c 是一种假设蛋白，在结核分枝杆菌 H37Ra 中，在酸性和营养应激下分别上调 25 倍和 4 倍。该蛋白质在最适 pH 8.0 和温度 40°C 下表现出 pNP-癸酸酯的脂肪分解活性。此外，该蛋白质还表现出磷脂酶活性。为了了解 rv2037c 对分枝杆菌生理学的影响，该基因被克隆并在耻垢分枝杆菌中表达。该蛋白质存在于膜和细胞外部分中。 rv2037c 在耻垢分枝杆菌 (MS_Rv2037c) 中的表达改变了集落形态和细胞表面特征，如增强的生物膜和薄膜形成。 MS_Rv2037c 降低细胞壁通透性，增强 TDM 含量，增强对各种应激和抗生素的抵抗力。 MS_Rv2037c 在受感染的 THP-1 巨噬细胞中表现出更好的感染和细胞内存活能力。用 Rv2037c 处理的巨噬细胞表现出不规则的细胞膜。与对照组相比，感染 MS_Rv2037c 的小鼠肺、肝和脾脏中的细菌载量更高。 Rv2037c 诱导促炎细胞因子 TNF α 和 IL12 的产生，表明其在免疫调节中的作用。重组蛋白还在 EPTB 和 MDR-TB 患者中产生体液反应。结果表明了这种酶在分枝杆菌细胞壁调节、感染和细胞内存活中的听觉作用。 (C) 2020 年由 Elsevier B.V. 出版
The genome of Mycobacterium tuberculosis encode for several hypothetical proteins that needed to be characterized. Rv2037c, a hypothetical protein, was 25 and 4 folds upregulated under acidic and nutritive stress, respectively in M. tuberculosis H37Ra. The protein demonstrated lipolytic activity with pNP-decanoate with optimum pH 8.0 and temperature 40 degrees C. In addition, the protein demonstrated phospholipase activity. To understand the effect of rv2037c on mycobacterium physiology, the gene was cloned and expressed in M. smegmatis. The protein was found in membrane and extracellular fraction. The expression of rv2037c in M. smegmatis (MS_Rv2037c) altered colony morphology and cell surface features like enhanced biofilm and pellicle formation. MS_Rv2037c decreased cell-wall permeability, enhanced TDM content, resistance against various stresses and antibiotics. MS_Rv2037c demonstrated better infection and intracellular survival capability in infected THP-1 macrophage. Macrophages treated with Rv2037c demonstrated irregular cell membrane. Mice infected with MS_Rv2037c had higher bacterial load in lung, liver and spleen compared to control. Rv2037c induced the production of pro-inflammatory cytokines TNF alpha and IL12, suggesting its role in immune-modulation. Recombinant protein also generated humoral response in EPTB and MDR-TB patients. The results pointed towards the audal role of this enzyme in cell-wall modulation, infection and intracellular survival of mycobacterium. (C) 2020 Published by Elsevier B.V.