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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.
Mol Microbiol. 2011 Jun; 80(6):1637-56.MM

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+Show Affiliations

Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos 62210, Mexico.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21518393

Citation

Martínez, Luary C., et al. "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." Molecular Microbiology, vol. 80, no. 6, 2011, pp. 1637-56.
Martínez LC, Yakhnin H, Camacho MI, et al. 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. Mol Microbiol. 2011;80(6):1637-56.
Martínez, L. C., Yakhnin, H., Camacho, M. I., Georgellis, D., Babitzke, P., Puente, J. L., & Bustamante, V. H. (2011). 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. Molecular Microbiology, 80(6), 1637-56. https://doi.org/10.1111/j.1365-2958.2011.07674.x
Martínez LC, et al. 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. Mol Microbiol. 2011;80(6):1637-56. PubMed PMID: 21518393.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Martínez,Luary C, AU - Yakhnin,Helen, AU - Camacho,Martha I, AU - Georgellis,Dimitris, AU - Babitzke,Paul, AU - Puente,José L, AU - Bustamante,Víctor H, Y1 - 2011/05/12/ PY - 2011/4/27/entrez PY - 2011/4/27/pubmed PY - 2011/12/13/medline SP - 1637 EP - 56 JF - Molecular microbiology JO - Mol Microbiol VL - 80 IS - 6 N2 - 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. SN - 1365-2958 UR - https://www.unboundmedicine.com/medline/citation/21518393/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_ L2 - https://doi.org/10.1111/j.1365-2958.2011.07674.x DB - PRIME DP - Unbound Medicine ER -