A rapid change in virulence gene expression during the transition from the intestinal lumen into tissue promotes systemic dissemination of Salmonella

PLoS Pathog. 2010 Aug 19;6(8):e1001060. doi: 10.1371/journal.ppat.1001060.


Bacterial pathogens causing systemic disease commonly evolve from organisms associated with localized infections but differ from their close relatives in their ability to overcome mucosal barriers by mechanisms that remain incompletely understood. Here we investigated whether acquisition of a regulatory gene, tviA, contributed to the ability of Salmonella enterica serotype Typhi to disseminate from the intestine to systemic sites of infection during typhoid fever. To study the consequences of acquiring a new regulator by horizontal gene transfer, tviA was introduced into the chromosome of S. enterica serotype Typhimurium, a closely related pathogen causing a localized gastrointestinal infection in immunocompetent individuals. TviA repressed expression of flagellin, a pathogen associated molecular pattern (PAMP), when bacteria were grown at osmotic conditions encountered in tissue, but not at higher osmolarity present in the intestinal lumen. TviA-mediated flagellin repression enabled bacteria to evade sentinel functions of human model epithelia and resulted in increased bacterial dissemination to the spleen in a chicken model. Collectively, our data point to PAMP repression as a novel pathogenic mechanism to overcome the mucosal barrier through innate immune evasion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Blotting, Western
  • Cell Line
  • Chickens
  • Electrophoresis, Polyacrylamide Gel
  • Flagellin / biosynthesis
  • Flow Cytometry
  • Gene Expression
  • Gene Expression Regulation, Bacterial*
  • Humans
  • Immune Evasion
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology*
  • Mice
  • Mice, Inbred C57BL
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salmonella / genetics
  • Salmonella / immunology
  • Salmonella / pathogenicity*
  • Salmonella Infections, Animal / genetics*
  • Salmonella Infections, Animal / immunology
  • Transcription Factors / genetics*
  • Typhoid Fever / genetics
  • Typhoid Fever / immunology
  • Virulence / genetics


  • Bacterial Proteins
  • Transcription Factors
  • tviA protein, Salmonella typhi
  • Flagellin