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The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella.
PLoS Pathog. 2017 Jul; 13(7):e1006497.PP

Abstract

The evolution of bacterial pathogenicity, heavily influenced by horizontal gene transfer, provides new virulence factors and regulatory connections that alter bacterial phenotypes. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) are chromosomal regions that were acquired at different evolutionary times and are essential for Salmonella virulence. In the intestine of mammalian hosts, Salmonella expresses the SPI-1 genes that mediate its invasion to the gut epithelium. Once inside the cells, Salmonella down-regulates the SPI-1 genes and induces the expression of the SPI-2 genes, which favor its intracellular replication. The mechanism by which the invasion machinery is deactivated following successful invasion of host cells is not known. Here, we show that the SPI-2 encoded transcriptional regulator SsrB, which positively controls SPI-2, acts as a dual regulator that represses expression of SPI-1 during intracellular stages of infection. The mechanism of this SPI-1 repression by SsrB was direct and acts upon the hilD and hilA regulatory genes. The phenotypic effect of this molecular switch activity was a significant reduction in invasion ability of S. enterica serovar Typhimurium while promoting the expression of genes required for intracellular survival. During mouse infections, Salmonella mutants lacking SsrB had high levels of hilA (SPI-1) transcriptional activity whereas introducing a constitutively active SsrB led to significant hilA repression. Thus, our results reveal a novel SsrB-mediated mechanism of transcriptional crosstalk between SPI-1 and SPI-2 that helps Salmonella transition to the intracellular lifestyle.

Authors+Show Affiliations

Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México, México.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28704543

Citation

Pérez-Morales, Deyanira, et al. "The Transcriptional Regulator SsrB Is Involved in a Molecular Switch Controlling Virulence Lifestyles of Salmonella." PLoS Pathogens, vol. 13, no. 7, 2017, pp. e1006497.
Pérez-Morales D, Banda MM, Chau NYE, et al. The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella. PLoS Pathog. 2017;13(7):e1006497.
Pérez-Morales, D., Banda, M. M., Chau, N. Y. E., Salgado, H., Martínez-Flores, I., Ibarra, J. A., Ilyas, B., Coombes, B. K., & Bustamante, V. H. (2017). The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella. PLoS Pathogens, 13(7), e1006497. https://doi.org/10.1371/journal.ppat.1006497
Pérez-Morales D, et al. The Transcriptional Regulator SsrB Is Involved in a Molecular Switch Controlling Virulence Lifestyles of Salmonella. PLoS Pathog. 2017;13(7):e1006497. PubMed PMID: 28704543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella. AU - Pérez-Morales,Deyanira, AU - Banda,María M, AU - Chau,N Y Elizabeth, AU - Salgado,Heladia, AU - Martínez-Flores,Irma, AU - Ibarra,J Antonio, AU - Ilyas,Bushra, AU - Coombes,Brian K, AU - Bustamante,Víctor H, Y1 - 2017/07/13/ PY - 2017/01/12/received PY - 2017/06/28/accepted PY - 2017/08/18/revised PY - 2017/7/14/pubmed PY - 2017/9/19/medline PY - 2017/7/14/entrez SP - e1006497 EP - e1006497 JF - PLoS pathogens JO - PLoS Pathog VL - 13 IS - 7 N2 - The evolution of bacterial pathogenicity, heavily influenced by horizontal gene transfer, provides new virulence factors and regulatory connections that alter bacterial phenotypes. Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) are chromosomal regions that were acquired at different evolutionary times and are essential for Salmonella virulence. In the intestine of mammalian hosts, Salmonella expresses the SPI-1 genes that mediate its invasion to the gut epithelium. Once inside the cells, Salmonella down-regulates the SPI-1 genes and induces the expression of the SPI-2 genes, which favor its intracellular replication. The mechanism by which the invasion machinery is deactivated following successful invasion of host cells is not known. Here, we show that the SPI-2 encoded transcriptional regulator SsrB, which positively controls SPI-2, acts as a dual regulator that represses expression of SPI-1 during intracellular stages of infection. The mechanism of this SPI-1 repression by SsrB was direct and acts upon the hilD and hilA regulatory genes. The phenotypic effect of this molecular switch activity was a significant reduction in invasion ability of S. enterica serovar Typhimurium while promoting the expression of genes required for intracellular survival. During mouse infections, Salmonella mutants lacking SsrB had high levels of hilA (SPI-1) transcriptional activity whereas introducing a constitutively active SsrB led to significant hilA repression. Thus, our results reveal a novel SsrB-mediated mechanism of transcriptional crosstalk between SPI-1 and SPI-2 that helps Salmonella transition to the intracellular lifestyle. SN - 1553-7374 UR - https://www.unboundmedicine.com/medline/citation/28704543/The_transcriptional_regulator_SsrB_is_involved_in_a_molecular_switch_controlling_virulence_lifestyles_of_Salmonella_ L2 - https://dx.plos.org/10.1371/journal.ppat.1006497 DB - PRIME DP - Unbound Medicine ER -