title: Crosstalk between virulence loci: regulation of Salmonella enterica pathogenicity island 1 (SPI-1) by products of the std fimbrial operon.
abstract: Invasion of intestinal epithelial cells is a critical step in Salmonella infection and requires the expression of genes located in Salmonella pathogenicity island 1 (SPI-1). A key factor for SPI-1 expression is DNA adenine (Dam) methylation, which activates synthesis of the SPI-1 transcriptional activator HilD. Dam-dependent regulation of hilD is postranscriptional (and therefore indirect), indicating the involvement of unknown cell functions under Dam methylation control. A genetic screen has identified the std fimbrial operon as the missing link between Dam methylation and SPI-1. We show that all genes in the std operon are part of a single transcriptional unit, and describe three previously uncharacterized ORFs (renamed stdD, stdE, and stdF). We present evidence that two such loci (stdE and stdF) are involved in Dam-dependent control of Salmonella SPI-1: in a Dam(-) background, deletion of stdE or stdF suppresses SPI-1 repression; in a Dam(+) background, constitutive expression of StdE and/or StdF represses SPI-1. Repression of SPI-1 by products of std operon explains the invasion defect of Salmonella Dam(-) mutants, which constitutively express the std operon. Dam-dependent repression of std in the ileum may be required to permit invasion, as indicated by two observations: constitutive expression of StdE and StdF reduces invasion of epithelial cells in vitro (1,000 fold) and attenuates Salmonella virulence in the mouse model (>60 fold). In turn, crosstalk between std and SPI-1 may play a role in intestinal infections by preventing expression of SPI-1 in the caecum, an intestinal compartment in which the std operon is known to be expressed.
authors.affiliation: Departamento de Genética, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: López-Garrido
authors.forename: Josep
authors.initials: J
authors.lastname: Casadesús
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D005260:Female; D010861:Fimbriae, Bacterial / Q000235:genetics* / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D056426:Genetic Loci / Q000235:genetics; D044404:Genomic Islands / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009876:Operon / Q000235:genetics; D030781:Organisms, Genetically Modified; D012480:Salmonella Infections / Q000382:microbiology / Q000473:pathology; D019779:Salmonella enterica / Q000235:genetics*; D014774:Virulence / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins