title: Integration of a complex regulatory cascade involving the SirA/BarA and Csr global regulatory systems that controls expression of the Salmonella SPI-1 and SPI-2 virulence regulons through HilD.
abstract: Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) play key roles in the pathogenesis of Salmonella enterica. Previously, we showed that when Salmonella grows in Luria-Bertani medium, HilD, encoded in SPI-1, first induces the expression of hilA, located in SPI-1, and subsequently of the ssrAB operon, located in SPI-2. These genes code for HilA and the SsrA/B two-component system, the positive regulators of the SPI-1 and SPI-2 regulons respectively. In this study, we demonstrate that CsrA, a global regulatory RNA binding protein, post-transcriptionally regulates hilD expression by directly binding near the Shine-Dalgarno and translation initiation codon sequences of the hilD mRNA, preventing its translation and leading to its accelerated turnover. Negative regulation is counteracted by the global SirA/BarA two-component system, which directly activates the expression of CsrB and CsrC, two non-coding regulatory RNAs that sequester CsrA, thereby preventing it from binding to its target mRNAs. Our results illustrate the integration of global and specific regulators into a multifactorial regulatory cascade controlling the expression of virulence genes acquired by horizontal transfer events.
authors.affiliation: Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico.
authors.forename: Luary C
authors.initials: LC
authors.lastname: Martínez
authors.forename: Helen
authors.initials: H
authors.lastname: Yakhnin
authors.forename: Martha I
authors.initials: MI
authors.lastname: Camacho
authors.forename: Dimitris
authors.initials: D
authors.lastname: Georgellis
authors.forename: Paul
authors.initials: P
authors.lastname: Babitzke
authors.forename: José L
authors.initials: JL
authors.lastname: Puente
authors.forename: Víctor H
authors.initials: VH
authors.lastname: Bustamante
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015964:Gene Expression Regulation, Bacterial; D044404:Genomic Islands; D006801:Humans; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; C119660:HilD protein, Salmonella typhimurium; D012097:Repressor Proteins; C104847:SirA protein, Salmonella; D015534:Trans-Activators; D014157:Transcription Factors