Nutrient Deprivation Affects Salmonella Invasion and Its Interaction With the Gastrointestinal Microbiota

PLoS One. 2016 Jul 20;11(7):e0159676. doi: 10.1371/journal.pone.0159676. eCollection 2016.


Salmonella enterica serovar Typhimurium (S. Typhimurium) is a foodborne enteric pathogen and a major cause of gastroenteritis in humans. It is known that molecules derived from the human fecal microbiota downregulate S. Typhimurium virulence gene expression and induce a starvation-like response. In this study, S. Typhimurium was cultured in minimal media to mimic starvation conditions such as that experienced by S. Typhimurium in the human intestinal tract, and the pathogen's virulence in vitro and in vivo was measured. S. Typhimurium cultured in minimal media displayed a reduced ability to invade human epithelial cells in a manner that was at least partially independent of the Salmonella Pathogenicity Island 1 (SPI-1) type III secretion system. Nutrient deprivation did not, however, alter the ability of S. Typhimurium to replicate and survive inside epithelial cells. In a murine model of S. Typhimurium-induced gastroenteritis, prior cultivation in minimal media did not alter the pathogen's ability to colonize mice, nor did it affect levels of gastrointestinal inflammation. Upon examining the post-infection fecal gastrointestinal microbiota, we found that specifically in the 129Sv/ImJ murine strain S. Typhimurium cultured in minimal media induced differential microbiota compositional shifts compared to that of S. Typhimurium cultured in rich media. Together these findings demonstrate that S. Typhimurium remains a potent pathogen even in the face of nutritional deprivation, but nevertheless that nutrient deprivation encountered in this environment elicits significant changes in the bacterium genetic programme, as well as its capacity to alter host microbiota composition.

MeSH terms

  • Animals
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Feces / microbiology
  • Gastroenteritis / diet therapy*
  • Gastroenteritis / genetics
  • Gastroenteritis / microbiology
  • Gastrointestinal Microbiome / genetics*
  • Gene Expression Regulation, Bacterial
  • Genomic Islands / genetics*
  • Humans
  • Intestines / microbiology
  • Intestines / pathology
  • Mice
  • Salmonella Infections / diet therapy*
  • Salmonella Infections / microbiology
  • Salmonella typhimurium / genetics*
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / pathogenicity
  • Starvation / metabolism
  • Starvation / pathology


  • Bacterial Proteins

Grant support

The work in BBF lab is funded by Canadian Institutes of Health Research (CIHR-27R18706). LCMA was supported by a fellowship from the Science without Borders program of the National Council of Technological and Scientific Development (CNPq-Brazil). YV was supported by a fellowship from the Michael Smith Foundation for Health research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.