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SseL, a Salmonella deubiquitinase required for macrophage killing and virulence

Author:
Rytkönen, Anne, Poh, John, Garmendia, Junkal, Boyle, Cliona, Thompson, Arthur, Liu, Mei, Freemont, Paul, Hinton, Jay C.D., Holden, David W.
Source:
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.9 pp. 3502-3507
ISSN:
0027-8424
Subject:
Salmonella Typhimurium, bacteria, cysteine proteinases, cytokines, cytotoxicity, macrophages, mice, mutants, pathogenicity islands, regulon, secretion, transcriptomics, type III secretion system, ubiquitin, virulence
Abstract:
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.
Agid:
2351802