Granzyme B Disrupts Central Metabolism and Protein Synthesis in Bacteria to Promote an Immune Cell Death Program.
Granzyme B Disrupts Central Metabolism and Protein Synthesis in Bacteria to Promote an Immune Cell Death Program.
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DOI：
10.1016/j.cell.2017.10.004
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发表时间：
2017-11-16
期刊：
影响因子：
64.5
通讯作者：
Lieberman J
中科院分区：
文献类型：
--
作者：
Dotiwala F;Sen Santara S;Binker-Cosen AA;Li B;Chandrasekaran S;Lieberman J
人类细胞毒性淋巴细胞杀死细胞内微生物。细胞毒性淋巴细胞释放的细胞毒性颗粒酶蛋白酶通过破坏电子传递、产生超氧阴离子和灭活细菌的氧化防御来触发细菌的氧化性死亡。然而，它们也会导致非氧化性细胞死亡，因为厌氧细菌也会被杀死。在这里，我们使用差异蛋白质组学鉴定了三种不相关的细菌，大肠杆菌，单核细胞增生李斯特菌和结核分枝杆菌的颗粒酶B底物。颗粒酶B在这三种细菌中都能切割一组高度保守的蛋白质，这些蛋白质在重要的生物合成和代谢途径中发挥作用，这些途径对细菌在各种环境条件下的生存至关重要。蛋白质合成、折叠和降解所需的关键蛋白质也是底物，包括多种氨基酰基tRNA合成酶、核糖体蛋白、蛋白质伴侣蛋白和Clp系统。因为杀伤细胞使用多管齐下的策略来瞄准重要途径，细菌可能不容易抵抗杀伤细胞的攻击。
Human cytotoxic lymphocytes kill intracellular microbes. The cytotoxic granule granzyme proteases released by cytotoxic lymphocytes trigger oxidative bacterial death by disrupting electron transport, generating superoxide anion and inactivating bacterial oxidative defenses. However, they also cause non-oxidative cell death, since anaerobic bacteria are also killed. Here we use differential proteomics to identify granzyme B substrates in three unrelated bacteria, Escherichia coli, Listeria monocytogenes and Mycobacteria tuberculosis. Granzyme B cleaves a highly conserved set of proteins in all three bacteria, which function in vital biosynthetic and metabolic pathways that are critical for bacterial survival under diverse environmental conditions. Key proteins required for protein synthesis, folding and degradation are also substrates, including multiple aminoacyl tRNA synthetases, ribosomal proteins, protein chaperones and the Clp system. Because killer cells use a multi-pronged strategy to target vital pathways, bacteria may not easily become resistant to killer cell attack.
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作者：
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通讯作者：
Lieberman J