title: In silico clustering of Salmonella global gene expression data reveals novel genes co-regulated with the SPI-1 virulence genes through HilD.
abstract: A wide variety of Salmonella enterica serovars cause intestinal and systemic infections to humans and animals. Salmonella Patogenicity Island 1 (SPI-1) is a chromosomal region containing 39 genes that have crucial virulence roles. The AraC-like transcriptional regulator HilD, encoded in SPI-1, positively controls the expression of the SPI-1 genes, as well as of several other virulence genes located outside SPI-1. In this study, we applied a clustering method to the global gene expression data of S. enterica serovar Typhimurium from the COLOMBOS database; thus genes that show an expression pattern similar to that of SPI-1 genes were selected. This analysis revealed nine novel genes that are co-expressed with SPI-1, which are located in different chromosomal regions. Expression analyses and protein-DNA interaction assays showed regulation by HilD for six of these genes: gtgE, phoH, sinR, SL1263 (lpxR) and SL4247 were regulated directly, whereas SL1896 was regulated indirectly. Interestingly, phoH is an ancestral gene conserved in most of bacteria, whereas the other genes show characteristics of genes acquired by Salmonella. A role in virulence has been previously demonstrated for gtgE, lpxR and sinR. Our results further expand the regulon of HilD and thus identify novel possible Salmonella virulence genes.
authors.affiliation: Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
authors.forename: Irma
authors.initials: I
authors.lastname: Martínez-Flores
authors.affiliation: Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
authors.forename: Deyanira
authors.initials: D
authors.lastname: Pérez-Morales
authors.affiliation: Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
authors.forename: Mishael
authors.initials: M
authors.lastname: Sánchez-Pérez
authors.affiliation: Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Paredes
authors.affiliation: Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
authors.forename: Julio
authors.initials: J
authors.lastname: Collado-Vides
authors.affiliation: Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
authors.forename: Heladia
authors.initials: H
authors.lastname: Salgado
authors.affiliation: Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, México.
authors.forename: Víctor H
authors.initials: VH
authors.lastname: Bustamante
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D020869:Gene Expression Profiling / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D006801:Humans; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics*; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C119660:HilD protein, Salmonella typhimurium; C419942:Spi1 protein, Salmonella; D014157:Transcription Factors; D037521:Virulence Factors