Article | Published:

Dietary trehalose enhances virulence of epidemic Clostridium difficile

Nature volume 553, pages 291294 (18 January 2018) | Download Citation

Abstract

Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.

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Acknowledgements

This work was supported by the National Institutes of Health (U01AI124290-01 and 5U19AI09087202). We thank the members of the Ostomy Association of Greater Lansing for anonymously donating samples, and D. Lyras for the RT244 strains. We thank V. Young, D. Mills, J. Walter and M. Costa-Mattioli for comments on the manuscript.

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Affiliations

  1. Baylor College of Medicine, Department of Molecular Virology and Microbiology, One Baylor Plaza, Houston, Texas 77030, USA

    • J. Collins
    • , H. Danhof
    • , J. M. Auchtung
    •  & R. A. Britton
  2. University of Oregon, Institute for Molecular Biology, 1318 Franklin Boulevard, Eugene, Oregon 97403, USA

    • C. Robinson
  3. Leiden University Medical Centre, Department of Medical Microbiology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands

    • C. W. Knetsch
    •  & H. C. van Leeuwen
  4. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK

    • T. D. Lawley

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Contributions

Concept and design of study: R.A.B., J.M.A., J.C. and C.R. Experiments: C. difficile growth, J.C. and C.R.; identification of L172I SNP and comparative analysis, C.R. and J.C.; treA RT–qPCR, H.D.; mouse infection model, J.C.; genetic manipulation of C. difficile strains, J.C. and C.R.; identification of RT078 trehalose insertion, C.W.K., H.C.L. and T.D.L.; faecal minibioreactor competitions, J.M.A.; spontaneous C. difficile mutant identification, H.D.; analysis, J.C., C.R., H.D., J.M.A. and R.B. The manuscript was drafted by J.C., J.M.A., and R.A.B., and revised by all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to R. A. Britton.

Reviewer Information Nature thanks J. Ballard, E. Pamer and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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https://doi.org/10.1038/nature25178

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