title: Salmonella effectors within a single pathogenicity island are differentially expressed and translocated by separate type III secretion systems.
abstract: Pathogenicity islands (PAIs) are large DNA segments in the genomes of bacterial pathogens that encode virulence factors. Five PAIs have been identified in the Gram-negative bacterium Salmonella enterica. Two of these PAIs, Salmonella pathogenicity island (SPI)-1 and SPI-2, encode type III secretion systems (TTSS), which are essential virulence determinants. These 'molecular syringes' inject effectors directly into the host cell, whereupon they manipulate host cell functions. These effectors are either encoded with their respective TTSS or scattered elsewhere on the Salmonella chromosome. Importantly, SPI-1 and SPI-2 are expressed under distinct environmental conditions: SPI-1 is induced upon initial contact with the host cell, whereas SPI-2 is induced intracellularly. Here, we demonstrate that a single PAI, in this case SPI-5, can encode effectors that are induced by distinct regulatory cues and targeted to different TTSS. SPI-5 encodes the SPI-1 TTSS translocated effector, SigD/SopB. In contrast, we report that the adjacently encoded effector PipB is part of the SPI-2 regulon. PipB is translocated by the SPI-2 TTSS to the Salmonella-containing vacuole and Salmonella-induced filaments. We also show that regions of SPI-5 are not conserved in all Salmonella spp. Although sigD/sopB is present in all Salmonella spp., pipB is not found in Salmonella bongori, which also lacks a functional SPI-2 TTSS. Thus, we demonstrate a functional and regulatory cross-talk between three chromosomal PAIs, SPI-1, SPI-2 and SPI-5, which has significant implications for the evolution and role of PAIs in bacterial pathogenesis.
authors.affiliation: Biotechnology Laboratory, Room 237, 6174 University Blvd, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
authors.forename: Leigh A
authors.initials: LA
authors.lastname: Knodler
authors.forename: Jean
authors.initials: J
authors.lastname: Celli
authors.forename: Wolf-Dietrich
authors.initials: WD
authors.lastname: Hardt
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.forename: Calvin
authors.initials: C
authors.lastname: Yip
authors.forename: B Brett
authors.initials: BB
authors.lastname: Finlay
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D005260:Female; D005455:Fluorescent Antibody Technique; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D017422:Sequence Analysis, DNA; D014774:Virulence
chemical_list: D001426:Bacterial Proteins