Department of Biotechnology, Panjab University, BMS Block-1, South Campus, Chandigarh, 160014, India.
Curr Microbiol. 2023 Jul 4;80(8):267. doi: 10.1007/s00284-023-03360-7.
The modulation of host's immune response plays an important role in the intracellular survival of Mycobacterium tuberculosis. The intracellular pathogen counteracts environmental stresses with help of the expression of several genes. The M. tuberculosis genome encodes several immune-modulatory proteins including PE (proline-glutamic acid)/PPE (proline-proline-glutamic acid) superfamily proteins. It is unclear how the unique PE/PPE proteins superfamily contributes to survival under different stress and pathophysiology conditions. Previously, we showed that PPE63 (Rv3539) has C-terminal esterase extension and was localized as a membrane attached and in extracellular compartment. Therefore, the probability of these proteins interacting with the host to modulate the host immune response cannot be ruled out. The physiological role of PPE63 was characterized by expressing the PPE63 in the M. smegmatis, a non-pathogenic strain intrinsically deficient of PPE63. The recombinant M. smegmatis expressing PPE63 altered the colony morphology, lipid composition, and integrity of the cell wall. It provided resistance to multiple hostile environmental stress conditions and several antibiotics. MS_Rv3539 demonstrated higher infection and intracellular survival in comparison to the MS_Vec in the PMA-differentiated THP-1 cells. The decreased intracellular level of ROS, NO, and expression of iNOS was observed in THP-1 cells upon infection with MS_Rv3539 in comparison to MS_Vec. Further, the decrease in expression of pro-inflammatory cytokines like IL-6, TNF-α, and IL-1β and enhanced anti-inflammatory cytokines like IL-10, pointed toward its role in immune modulation. Overall this study suggested the role of Rv3539 in enhanced intracellular survival of M. smegmatis via cell wall modulation and altered immune response of host.
宿主免疫反应的调节在结核分枝杆菌的细胞内生存中起着重要作用。这种细胞内病原体通过表达几种基因来对抗环境压力。结核分枝杆菌基因组编码几种免疫调节蛋白，包括 PE（脯氨酸-谷氨酸）/PPE（脯氨酸-脯氨酸-谷氨酸）超家族蛋白。目前尚不清楚独特的 PE/PPE 蛋白超家族如何在不同的应激和病理生理条件下有助于生存。以前，我们发现 PPE63（Rv3539）具有 C 端酯酶延伸，并且定位于膜附着和细胞外区室。因此，这些蛋白质与宿主相互作用以调节宿主免疫反应的可能性不能排除。通过在缺乏 PPE63 的非致病性菌株 M. smegmatis 中表达 PPE63，来表征 PPE63 的生理作用。表达 PPE63 的重组 M. smegmatis 改变了菌落形态、脂质组成和细胞壁完整性。它对多种恶劣的环境应激条件和几种抗生素具有抗性。与 MS_Vec 相比，MS_Rv3539 在 PMA 分化的 THP-1 细胞中的感染和细胞内生存能力更高。与 MS_Vec 相比，THP-1 细胞感染 MS_Rv3539 时，细胞内 ROS、NO 和 iNOS 的表达减少。此外，与 MS_Vec 相比，促炎细胞因子如 IL-6、TNF-α 和 IL-1β 的表达减少，抗炎细胞因子如 IL-10 的表达增强，表明其在免疫调节中的作用。总的来说，这项研究表明 Rv3539 通过细胞壁调节和宿主免疫反应改变，在增强 M. smegmatis 的细胞内生存中起作用。
