Patil Veerupaxagouda, Kumar Anujith, Kuruppath Sanjana, Nandi Dipankar
Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, India.
FEMS Immunol Med Microbiol. 2007 Nov;51(2):431-42. doi: 10.1111/j.1574-695X.2007.00323.x. Epub 2007 Sep 18.
The cytosolic protein degradation pathway, involving ATP-dependent proteases and ATP-independent peptidases, is important for modulating several cellular responses. The involvement of pathogen-encoded ATP-dependent proteases is well established during infection. However, the roles of ATP-independent peptidases in this process are not well studied. The functional role of Peptidase N (PepN), an ATP-independent enzyme belonging to the M1 family, during systemic infection of mice by Salmonella enterica serovar Typhimurium (Salmonella typhimurium) was investigated. In a systemic model of infection, the number of CFU of S. typhimurium containing a targeted deletion in peptidase N (DeltapepN), compared with wild type, was significantly higher in the lymph node and spleen. In addition, S. typhimurium replicated in the thymus and greatly reduced the number of immature CD4(+)CD8(+) thymocytes in a dose- and time-dependent manner. Strains lacking or overexpressing pepN were used to show that the reduction in the number of thymocytes, but not lymph node cells, depends on a critical number of CFU. These findings establish a role for PepN in reducing the in vivo CFU of S. typhimurium during systemic infection. The implications of these results, in the context of the roles of proteases and peptidases, during host-pathogen interactions are discussed.
涉及ATP依赖性蛋白酶和非ATP依赖性肽酶的胞质蛋白降解途径，对于调节多种细胞反应很重要。病原体编码的ATP依赖性蛋白酶在感染过程中的作用已得到充分证实。然而，非ATP依赖性肽酶在这一过程中的作用尚未得到充分研究。研究了肽酶N（PepN），一种属于M1家族的非ATP依赖性酶，在鼠伤寒沙门氏菌对小鼠的全身感染过程中的功能作用。在全身感染模型中，与野生型相比，肽酶N基因靶向缺失的鼠伤寒沙门氏菌（DeltapepN）在淋巴结和脾脏中的CFU数量显著更高。此外，鼠伤寒沙门氏菌在胸腺中复制，并以剂量和时间依赖性方式大幅减少未成熟CD4(+)CD8(+)胸腺细胞的数量。使用缺乏或过表达pepN的菌株表明，胸腺细胞而非淋巴结细胞数量的减少取决于一定数量的CFU。这些发现确立了PepN在全身感染期间减少鼠伤寒沙门氏菌体内CFU的作用。本文讨论了这些结果在蛋白酶和肽酶作用背景下，在宿主-病原体相互作用中的意义。
