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Dietary trehalose enhances virulence of epidemic Clostridium difficile.
Nature 2018; 553(7688):291-294Nat

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.

Authors+Show Affiliations

Baylor College of Medicine, Department of Molecular Virology and Microbiology, One Baylor Plaza, Houston, Texas 77030, USA.University of Oregon, Institute for Molecular Biology, 1318 Franklin Boulevard, Eugene, Oregon 97403, USA.Baylor College of Medicine, Department of Molecular Virology and Microbiology, One Baylor Plaza, Houston, Texas 77030, USA.Leiden University Medical Centre, Department of Medical Microbiology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.Leiden University Medical Centre, Department of Medical Microbiology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.Baylor College of Medicine, Department of Molecular Virology and Microbiology, One Baylor Plaza, Houston, Texas 77030, USA.Baylor College of Medicine, Department of Molecular Virology and Microbiology, One Baylor Plaza, Houston, Texas 77030, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29310122

Citation

Collins, J, et al. "Dietary Trehalose Enhances Virulence of Epidemic Clostridium Difficile." Nature, vol. 553, no. 7688, 2018, pp. 291-294.
Collins J, Robinson C, Danhof H, et al. Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature. 2018;553(7688):291-294.
Collins, J., Robinson, C., Danhof, H., Knetsch, C. W., van Leeuwen, H. C., Lawley, T. D., ... Britton, R. A. (2018). Dietary trehalose enhances virulence of epidemic Clostridium difficile. Nature, 553(7688), pp. 291-294. doi:10.1038/nature25178.
Collins J, et al. Dietary Trehalose Enhances Virulence of Epidemic Clostridium Difficile. Nature. 2018 01 18;553(7688):291-294. PubMed PMID: 29310122.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary trehalose enhances virulence of epidemic Clostridium difficile. AU - Collins,J, AU - Robinson,C, AU - Danhof,H, AU - Knetsch,C W, AU - van Leeuwen,H C, AU - Lawley,T D, AU - Auchtung,J M, AU - Britton,R A, Y1 - 2018/01/03/ PY - 2017/05/26/received PY - 2017/11/28/accepted PY - 2018/1/9/pubmed PY - 2018/5/4/medline PY - 2018/1/9/entrez SP - 291 EP - 294 JF - Nature JO - Nature VL - 553 IS - 7688 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/29310122/Dietary_trehalose_enhances_virulence_of_epidemic_Clostridium_difficile_ L2 - http://dx.doi.org/10.1038/nature25178 DB - PRIME DP - Unbound Medicine ER -