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 because 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 multipronged strategy to target vital pathways, bacteria may not easily become resistant to killer cell attack.

中文翻译：

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颗粒酶B破坏细菌的中枢代谢和蛋白质合成，从而促进免疫细胞死亡程序。

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粒酶蛋白酶通过破坏电子传递，产生超氧阴离子和使细菌的氧化防御失活来触发氧化细菌的死亡。但是，它们也引起非氧化性细胞死亡，因为厌氧细菌也被杀死。在这里，我们使用差异蛋白质组学来鉴定三种不相关细菌中的颗粒酶B底物：大肠杆菌，单核细胞增生性李斯特菌和结核分枝杆菌。颗粒酶B在所有三种细菌中均裂解出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起作用，这些途径对于细菌在各种环境条件下的存活至关重要。蛋白质合成，折叠和降解所需的关键蛋白质也是底物，包括多种氨酰基tRNA合成酶，核糖体蛋白，蛋白伴侣和Clp系统。由于杀伤细胞采用多管齐下的策略来靶向重要途径，因此细菌可能不容易对杀伤细胞的攻击产生抵抗力。