Dietary trehalose enhances virulence of epidemic Clostridium difficile

J Collins; C Robinson; H Danhof; C W Knetsch; H C van Leeuwen; T D Lawley; J M Auchtung; R A Britton

doi:10.1038/nature25178

Dietary trehalose enhances virulence of epidemic Clostridium difficile

Nature. 2018 Jan 18;553(7688):291-294. doi: 10.1038/nature25178. Epub 2018 Jan 3.

Authors

J Collins¹, C Robinson², H Danhof¹, C W Knetsch³, H C van Leeuwen³, T D Lawley⁴, J M Auchtung¹, R A Britton¹

Affiliations

¹ Baylor College of Medicine, Department of Molecular Virology and Microbiology, One Baylor Plaza, Houston, Texas 77030, USA.
² University of Oregon, Institute for Molecular Biology, 1318 Franklin Boulevard, Eugene, Oregon 97403, USA.
³ Leiden University Medical Centre, Department of Medical Microbiology, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
⁴ Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Bacterial Proteins / genetics
Bacterial Proteins / metabolism
Clostridioides difficile / drug effects*
Clostridioides difficile / genetics
Clostridioides difficile / metabolism
Clostridioides difficile / pathogenicity*
Clostridium Infections / epidemiology*
Clostridium Infections / microbiology*
Dietary Sugars / administration & dosage
Dietary Sugars / metabolism
Dietary Sugars / pharmacology*
Female
Gastrointestinal Microbiome
Humans
Male
Mice
Mice, Inbred C57BL
Multigene Family
Phosphoenolpyruvate Sugar Phosphotransferase System / genetics
Phosphoenolpyruvate Sugar Phosphotransferase System / metabolism
Point Mutation
Repressor Proteins / genetics
Repressor Proteins / metabolism
Ribotyping
Trehalose / administration & dosage
Trehalose / metabolism
Trehalose / pharmacology*
Virulence / drug effects*

Substances

Bacterial Proteins
Dietary Sugars
Repressor Proteins
trehalose repressor protein, bacteria
Trehalose
Phosphoenolpyruvate Sugar Phosphotransferase System

Abstract

Publication types

MeSH terms

Substances

Grants and funding