The transcriptional regulator SsrB is involved in a molecular switch controlling virulence lifestyles of Salmonella

PLoS Pathog. 2017 Jul 13;13(7):e1006497. doi: 10.1371/journal.ppat.1006497. eCollection 2017 Jul.


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.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Genomic Islands
  • Humans
  • Mice
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*
  • Salmonella typhimurium / pathogenicity*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Virulence


  • Bacterial Proteins
  • SsrB protein, Salmonella typhimurium
  • Transcription Factors

Grants and funding

This work was supported by grants from Consejo Nacional de Ciencia y Tecnología (CONACYT) / México (179071 and 254531 to VHB), from Dirección General de Asuntos del Personal Académico de la UNAM / México (IN203415 to VHB), from the Canadian Institutes of Health Research (MOP 82704 to BKC), from the Canada Foundation for Innovation (to BKC), and from the Canada Research Chairs program (to BKC). DPM was supported by a grant from CONACYT (179071). MMB was supported by fellowships from CONACYT (334063 and 403748). NYEC is the recipient of an Ontario Graduate Scholarship. BKC is the Canada Research Chair in Infectious Disease Pathogenesis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.