Pathogenicity of Salmonella enterica in Caenorhabditis elegans relies on disseminated oxidative stress in the infected host

PLoS One. 2012;7(9):e45417. doi: 10.1371/journal.pone.0045417. Epub 2012 Sep 28.

Abstract

Feeding Caenorhabditis elegans with Salmonella enterica serovar Typhimurium significantly shortens the lifespan of the nematode. S. Typhimurium-infected C. elegans, stained with 2',7'-dichlorodihydrofluorescein diacetate which fluoresces upon exposure to reactive oxygen species, revealed intestinal luminal staining that along with the time of infection progressed to a strong staining in the hypodermal tissues of the nematode. Still, we could not detect invasion beyond the nematode's intestinal epithelium at any stage of the infection. A similar dispersion of oxidative response was also noted in nematodes infected with S. Dublin, but not with non-pathogenic Escherichia coli or the defined pathogen Burkholderia thailandensis. Addition of catalase or the reductant ascorbic acid significantly restored the lifespan of S. Typhimurium-infected nematodes. Mutational inactivation of the bacterial thioredoxin 1 resulted in total ablation of the hypodermal oxidative response to infection, and in a strong attenuation of virulence. Virulence of the thioredoxin 1 mutant was restored by trans-complementation with redox-active variants of thioredoxin 1 or, surprisingly, by exposing the thioredoxin 1 mutant to sublethal concentrations of the disulphide catalyst copper chloride prior to infection. In summary, our observations define a new aspect in virulence of S. enterica that apparently does not involve the classical invasive or intracellular phenotype of the pathogen, but that depends on the ability to provoke overwhelming systemic oxidative stress in the host through the redox activity of bacterial thioredoxin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans / microbiology*
  • Copper / pharmacology
  • Escherichia coli / drug effects
  • Escherichia coli / physiology
  • Intestinal Mucosa / metabolism
  • Intestines / microbiology
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism
  • Salmonella enterica / drug effects
  • Salmonella enterica / pathogenicity*
  • Virulence / drug effects

Substances

  • Reactive Oxygen Species
  • Copper

Grant support

This study was supported by research grants from the Swedish Medical Research Council to MR. XS is a Ph.D. fellow of Agency for Science, Technology and Research, Singapore. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.