title: Salmonella SsrB activates a global regulon of horizontally acquired genes.
abstract: Salmonella enterica is a bacterial pathogen of humans that can proliferate within epithelial cells as well as professional phagocytes of the immune system. This ability requires an S. enterica specific locus termed Salmonella pathogenicity island 2 (SPI-2). SPI-2 encodes a type III secretion system that injects effectors encoded within the island into host cell cytosol to promote virulence. SsrAB is a two-component regulator encoded within SPI-2 that was assumed to activate SPI-2 genes exclusively. Here, it is shown that SsrB in fact activates a global regulon. At least 10 genes outside SPI-2 are SsrB regulated within epithelial and macrophage cells. Nine of these 10 SsrB-regulated genes outside SPI-2 reside within previously undescribed regions of the Salmonella genome. Most share no sequence homology with current database entries. However, one is remarkably homologous to human glucosyl ceramidase, an enzyme involved in the ceramide signalling pathway. The SsrB regulon is modulated by the two-component regulatory systems PhoP/PhoQ and OmpR/EnvZ, and is upregulated in the intracellular microenvironment.
authors.affiliation: Department of Microbiology, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201, USA. worleym@ohsu.edu
authors.forename: M J
authors.initials: MJ
authors.lastname: Worley
authors.forename: K H
authors.initials: KH
authors.lastname: Ching
authors.forename: F
authors.initials: F
authors.lastname: Heffron
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D005962:Glucosylceramidase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010586:Phagocytes / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D018085:Regulon / Q000235:genetics*; D015183:Restriction Mapping; D019779:Salmonella enterica / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000382:microbiology; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; D011993:Recombinant Fusion Proteins; C119761:SsrB protein, Salmonella typhimurium; D014157:Transcription Factors; D005962:Glucosylceramidase