Gut inflammation provides a respiratory electron acceptor for Salmonella (original) (raw)

Nature volume 467, pages 426–429 (2010)Cite this article

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Abstract

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen.

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Acknowledgements

We thank H. Chu for providing real-time PCR primers, V. Tolstikov for performing the liquid chromatography–mass spectrometry analysis, M. Xavier for assistance with histopathology and V. Gerriets for technical assistance. Work in A.J.B.’s laboratory is supported by Public Health Service grants AI040124, AI044170, AI073120, AI076246 and AI088122. P.T. was supported by a stipend from the Department of Microbiology, Chiang Mai University, Thailand.

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Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, One Shields Avenue, Davis, California 95616, USA,
    Sebastian E. Winter, Parameth Thiennimitr, Maria G. Winter, Brian P. Butler, Robert W. Crawford, Joseph M. Russell, Charles L. Bevins, Renée M. Tsolis & Andreas J. Bäumler
  2. Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
    Parameth Thiennimitr
  3. Department of Microbiology, University of California, Davis, One Shields Avenue, Davis, California 95616, USA,
    Douglas L. Huseby & John R. Roth
  4. Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, 77843, Texas, USA
    L. Garry Adams

Authors

  1. Sebastian E. Winter
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  2. Parameth Thiennimitr
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  3. Maria G. Winter
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  4. Brian P. Butler
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  5. Douglas L. Huseby
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  6. Robert W. Crawford
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  7. Joseph M. Russell
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  8. Charles L. Bevins
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  9. L. Garry Adams
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  10. Renée M. Tsolis
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  11. John R. Roth
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  12. Andreas J. Bäumler
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Contributions

S.E.W. contributed to the experimental design, constructed bacterial strains and contributed to Figs 1c–e, 2c, d, 3d, e and Supplementary Figs 1a, b, e, f and 3. P.T. contributed to Fig. 1f and Supplementary Fig. 1c, d and assisted with mouse experiments. M.G.W. assisted with mouse experiments and performed cloning experiments. B.P.B. contributed to Figs 1b , 2a, b, 3b, c and Supplementary Fig. 2. D.L.H. constructed bacterial strains. R.W.C. and J.M.R. contributed to Fig. 3a. L.G.A. performed the ligated loop surgery. C.L.B., L.G.A., R.M.T., J.R.R. and A.J.B. provided financial support for the study and contributed to the experimental design. S.E.W. and A.J.B. were responsible for the overall study design and for writing the manuscript.

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Correspondence toAndreas J. Bäumler.

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The authors declare no competing financial interests.

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Supplementary Information

This file contains Supplementary Figures 1-3 with legends, Supplementary Methods, Supplementary Tables 1-2 and additional references. (PDF 334 kb)

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Winter, S., Thiennimitr, P., Winter, M. et al. Gut inflammation provides a respiratory electron acceptor for Salmonella.Nature 467, 426–429 (2010). https://doi.org/10.1038/nature09415

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Editorial Summary

A gut pathogen gains an edge

The ability of the enteric pathogen Salmonella enterica serotype Typhimurium to use tetrathionate as a terminal electron acceptor has been used in the laboratory as a convenient means of enriching growth media containing this bacterium for many years. Tetrathionate respiration was thought to have little importance during infection, but to come into its own in free-living bacteria in environments containing tetrathionate, such as soil or decomposing carcasses. Now a possible role has been identified for this metabolism during intestinal infection. Acute intestinal inflammation induced by S. enterica Typhimurium virulence factors is shown to be accompanied by production of oxygen radicals in the gut lumen as part of the immune response. These oxygen radicals oxidize thiosulphate, the end product of hydrogen-sulphide detoxification by enterocytes, to tetrathionate. The pathogen can then use tetrathionate respiration during growth in the inflamed intestine, allowing it to out-compete other microbes that rely on anaerobic fermentation.

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