PMID:29107333

Citation	Dotiwala, F, Sen Santara, S, Binker-Cosen, AA, Li, B, Chandrasekaran, S and Lieberman, J (2017) Granzyme B Disrupts Central Metabolism and Protein Synthesis in Bacteria to Promote an Immune Cell Death Program. Cell 171:1125-1137.e11
Abstract	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.
Links	PubMed PMC5693722 Online version:10.1016/j.cell.2017.10.004
Keywords	Amino Acyl-tRNA Synthetases/metabolism; Animals; Escherichia coli/cytology; Escherichia coli/metabolism; Granzymes/metabolism; Humans; Killer Cells, Natural/enzymology; Killer Cells, Natural/immunology; Listeria monocytogenes/cytology; Listeria monocytogenes/metabolism; Metabolic Networks and Pathways; Mice; Mycobacterium tuberculosis/cytology; Mycobacterium tuberculosis/metabolism; Protein Biosynthesis; Proteomics; Ribosomes/metabolism; T-Lymphocytes, Cytotoxic/enzymology; T-Lymphocytes, Cytotoxic/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:GRAB		GO:0017148: negative regulation of translation	ECO:0000314:		P		Fig 3B shows that luminescence decreases of luciferase reporter gene with prolonged exposure to GZMB. This assay was performed with human GZMB exposed to E.Coli.	complete CACAO 13147

References

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