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SseL Is a Salmonella-Specific Translocated Effector Integrated into the SsrB-Controlled Salmonella Pathogenicity Island 2 Type III Secretion System

Brian K. Coombes,^1,2,* Michael J. Lowden,^3, Jennifer L. Bishop,³ Mark E. Wickham,³ Nat F. Brown,³ Nancy Duong,¹ Suzanne Osborne,¹ Ohad Gal-Mor,³ and B. Brett Finlay³

Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON,¹ Public Heath Agency of Canada, Laboratory for Foodborne Zoonoses, Guelph, ON,² Michael Smith Laboratories and Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada³

Received 21 June 2006/ Returned for modification 21 August 2006/ Accepted 29 November 2006

Bacterial pathogens use horizontal gene transfer to acquire virulence factors that influence host colonization, alter virulence traits, and ultimately shape the outcome of disease following infection. One hallmark of the host-pathogen interaction is the prokaryotic type III secretion system that translocates virulence factors into host cells during infection. Salmonella enterica possesses two type III secretion systems that are utilized during host colonization and intracellular replication. Salmonella pathogenicity island 2 (SPI2) is a genomic island containing approximately 30 contiguous genes required to assemble a functional secretion system including the two-component regulatory system called SsrA-SsrB that positively regulates transcription of the secretion apparatus. We used transcriptional profiling with DNA microarrays to search for genes that coregulate with the SPI2 type III secretion machinery in an SsrB-dependent manner. Here we report the identification of a Salmonella-specific translocated effector called SseL that is required for full virulence during murine typhoid-like disease. Analysis of infected macrophages using fluorescence-activated cell sorting revealed that sseL is induced inside cells and requires SsrB for expression. SseL is retained predominantly in the cytoplasm of infected cells following translocation by the type III system encoded in SPI2. Animal infection experiments with sseL mutant bacteria indicate that integration of SseL into the SsrB response regulatory system contributes to systemic virulence of this pathogen.

Published ahead of print on 11 December 2006.

Editor: V. J. DiRita

These authors contributed equally to this work.

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