SseL, a Salmonella deubiquitinase required for macrophage killing and virulence

Anne Rytkönen, John Poh, Junkal Garmendia, Cliona Boyle, Arthur Thompson, Mei Liu, Paul Freemont, Jay C.D. Hinton, David W. Holden*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

171 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3502-3507
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number9
DOIs
Publication statusPublished - 27 Feb 2007
Externally publishedYes

Keywords

  • Cytotoxicity
  • Deubiquitinating enzyme
  • SPI-2

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