Tags

Type your tag names separated by a space and hit enter

The two-component system CpxR/A represses the expression of Salmonella virulence genes by affecting the stability of the transcriptional regulator HilD.
Front Microbiol. 2015; 6:807.FM

Abstract

Salmonella enterica can cause intestinal or systemic infections in humans and animals mainly by the presence of pathogenicity islands SPI-1 and SPI-2, containing 39 and 44 genes, respectively. The AraC-like regulator HilD positively controls the expression of the SPI-1 genes, as well as many other Salmonella virulence genes including those located in SPI-2. A previous report indicates that the two-component system CpxR/A regulates the SPI-1 genes: the absence of the sensor kinase CpxA, but not the absence of its cognate response regulator CpxR, reduces their expression. The presence and absence of cell envelope stress activates kinase and phosphatase activities of CpxA, respectively, which in turn controls the level of phosphorylated CpxR (CpxR-P). In this work, we further define the mechanism for the CpxR/A-mediated regulation of SPI-1 genes. The negative effect exerted by the absence of CpxA on the expression of SPI-1 genes was counteracted by the absence of CpxR or by the absence of the two enzymes, AckA and Pta, which render acetyl-phosphate that phosphorylates CpxR. Furthermore, overexpression of the lipoprotein NlpE, which activates CpxA kinase activity on CpxR, or overexpression of CpxR, repressed the expression of SPI-1 genes. Thus, our results provide several lines of evidence strongly supporting that the absence of CpxA leads to the phosphorylation of CpxR via the AckA/Pta enzymes, which represses both the SPI-1 and SPI-2 genes. Additionally, we show that in the absence of the Lon protease, which degrades HilD, the CpxR-P-mediated repression of the SPI-1 genes is mostly lost; moreover, we demonstrate that CpxR-P negatively affects the stability of HilD and thus decreases the expression of HilD-target genes, such as hilD itself and hilA, located in SPI-1. Our data further expand the insight on the different regulatory pathways for gene expression involving CpxR/A and on the complex regulatory network governing virulence in Salmonella.

Authors+Show Affiliations

Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Centro Médico Nacional Siglo XX1-IMSS México DF, Mexico.Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México Cuernavaca, Morelos, Mexico.Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México Cuernavaca, Morelos, Mexico.Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México Cuernavaca, Morelos, Mexico.Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México Cuernavaca, Morelos, Mexico.Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México Cuernavaca, Morelos, Mexico.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26300871

Citation

De la Cruz, Miguel A., et al. "The Two-component System CpxR/A Represses the Expression of Salmonella Virulence Genes By Affecting the Stability of the Transcriptional Regulator HilD." Frontiers in Microbiology, vol. 6, 2015, p. 807.
De la Cruz MA, Pérez-Morales D, Palacios IJ, et al. The two-component system CpxR/A represses the expression of Salmonella virulence genes by affecting the stability of the transcriptional regulator HilD. Frontiers in microbiology. 2015;6:807.
De la Cruz, M. A., Pérez-Morales, D., Palacios, I. J., Fernández-Mora, M., Calva, E., & Bustamante, V. H. (2015). The two-component system CpxR/A represses the expression of Salmonella virulence genes by affecting the stability of the transcriptional regulator HilD. Frontiers in Microbiology, 6, 807. https://doi.org/10.3389/fmicb.2015.00807
De la Cruz MA, et al. The Two-component System CpxR/A Represses the Expression of Salmonella Virulence Genes By Affecting the Stability of the Transcriptional Regulator HilD. Frontiers in microbiology. 2015;6:807. PubMed PMID: 26300871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The two-component system CpxR/A represses the expression of Salmonella virulence genes by affecting the stability of the transcriptional regulator HilD. AU - De la Cruz,Miguel A, AU - Pérez-Morales,Deyanira, AU - Palacios,Irene J, AU - Fernández-Mora,Marcos, AU - Calva,Edmundo, AU - Bustamante,Víctor H, Y1 - 2015/08/06/ PY - 2015/05/07/received PY - 2015/07/22/accepted PY - 2015/8/25/entrez PY - 2015/8/25/pubmed PY - 2015/8/25/medline KW - CpxR/A KW - HilD KW - Lon KW - RpoH KW - SPI KW - Salmonella KW - regulation KW - virulence SP - 807 EP - 807 JF - Frontiers in microbiology VL - 6 N2 - Salmonella enterica can cause intestinal or systemic infections in humans and animals mainly by the presence of pathogenicity islands SPI-1 and SPI-2, containing 39 and 44 genes, respectively. The AraC-like regulator HilD positively controls the expression of the SPI-1 genes, as well as many other Salmonella virulence genes including those located in SPI-2. A previous report indicates that the two-component system CpxR/A regulates the SPI-1 genes: the absence of the sensor kinase CpxA, but not the absence of its cognate response regulator CpxR, reduces their expression. The presence and absence of cell envelope stress activates kinase and phosphatase activities of CpxA, respectively, which in turn controls the level of phosphorylated CpxR (CpxR-P). In this work, we further define the mechanism for the CpxR/A-mediated regulation of SPI-1 genes. The negative effect exerted by the absence of CpxA on the expression of SPI-1 genes was counteracted by the absence of CpxR or by the absence of the two enzymes, AckA and Pta, which render acetyl-phosphate that phosphorylates CpxR. Furthermore, overexpression of the lipoprotein NlpE, which activates CpxA kinase activity on CpxR, or overexpression of CpxR, repressed the expression of SPI-1 genes. Thus, our results provide several lines of evidence strongly supporting that the absence of CpxA leads to the phosphorylation of CpxR via the AckA/Pta enzymes, which represses both the SPI-1 and SPI-2 genes. Additionally, we show that in the absence of the Lon protease, which degrades HilD, the CpxR-P-mediated repression of the SPI-1 genes is mostly lost; moreover, we demonstrate that CpxR-P negatively affects the stability of HilD and thus decreases the expression of HilD-target genes, such as hilD itself and hilA, located in SPI-1. Our data further expand the insight on the different regulatory pathways for gene expression involving CpxR/A and on the complex regulatory network governing virulence in Salmonella. SN - 1664-302X UR - https://www.unboundmedicine.com/medline/citation/26300871/The_two_component_system_CpxR/A_represses_the_expression_of_Salmonella_virulence_genes_by_affecting_the_stability_of_the_transcriptional_regulator_HilD_ L2 - https://doi.org/10.3389/fmicb.2015.00807 DB - PRIME DP - Unbound Medicine ER -