SseL, a Salmonella deubiquitinase required for macrophage killing and virulence
| Autor: | Cliona Boyle, David W. Holden, Anne Rytkönen, John Poh, Mei Liu, Paul S. Freemont, Junkal Garmendia, Jay C. D. Hinton, Arthur Thompson |
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| Rok vydání: | 2007 |
| Předmět: |
Salmonella
Molecular Sequence Data Virulence Biology medicine.disease_cause Regulon Microbiology Deubiquitinating enzyme Type three secretion system Mice Bacterial Proteins Two-Hybrid System Techniques Endopeptidases medicine Animals Immunoprecipitation Secretion Amino Acid Sequence Oligonucleotide Array Sequence Analysis Immunoassay Multidisciplinary Effector Ubiquitin Macrophages Membrane Proteins Sequence Analysis DNA Biological Sciences biology.organism_classification Salmonella enterica biology.protein Mutagenesis Site-Directed Sequence Alignment Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 104(9) |
| ISSN: | 0027-8424 |
| Popis: | Expression of the Salmonella enterica serovar Typhimurium pathogenicity island 2 (SPI-2) type III secretion system is controlled by the two-component regulatory system SsrA-SsrB. We used a transcriptomic approach to help define the SsrA-SsrB regulon. We identified a gene encoding an uncharacterized effector (SseL) whose translocation into host cells depends on the SPI-2 secretion system. SseL has similarities to cysteine proteases with deubiquitinating activity. A GST-SseL fusion protein specifically hydrolyzed mono- and polyubiquitin substrates in vitro with a preference for K63-linked ubiquitin chains. Ubiquitin-modified proteins accumulated in macrophages infected with Salmonella sseL mutant strains but to a lesser extent when infected with bacteria expressing active protein, demonstrating that SseL functions as a deubiquitinase in vivo. Salmonella sseL mutant strains did not show a replication defect or induce altered levels of cytokine production upon infection of macrophages but were defective for a delayed cytotoxic effect and were attenuated for virulence in mice. |
| Databáze: | OpenAIRE |
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