Dietary trehalose enhances virulence of epidemic Clostridium difficile

• Published in: Nature (London) Vol. 553; no. 7688; pp. 291 - 294
• Main Authors: Collins, J., Robinson, C., Danhof, H., Knetsch, C. W., van Leeuwen, H. C., Lawley, T. D., Auchtung, J. M., Britton, R. A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.01.2018; Nature Publishing Group
• Subjects: 38/44; 38/70; 45/70; 631/326/107; 631/326/2565/855; 631/326/325/1506; 631/326/421; 64; 64/60; Analysis; Animals; Bacteria; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Clostridioides difficile - drug effects; Clostridioides difficile - genetics; Clostridioides difficile - metabolism; Clostridioides difficile - pathogenicity; Clostridium; Clostridium difficile; Clostridium Infections - epidemiology; Clostridium Infections - microbiology; Dietary Sugars - administration & dosage; Dietary Sugars - metabolism; Dietary Sugars - pharmacology; Emergence; Epidemics; Female; Food additives; Gastrointestinal Microbiome; Gene mutation; Genetic aspects; Genomes; Health aspects; Humanities and Social Sciences; Humans; Male; Metabolism; Mice; Mice, Inbred C57BL; Microbiota; multidisciplinary; Multigene Family; Mutation; Nosocomial infection; Permease; Phosphoenolpyruvate Sugar Phosphotransferase System - genetics; Phosphoenolpyruvate Sugar Phosphotransferase System - metabolism; Physiological aspects; Point Mutation; Repressor Proteins - genetics; Repressor Proteins - metabolism; Ribotyping; Science; Trehalose; Trehalose - administration & dosage; Trehalose - metabolism; Trehalose - pharmacology; Virulence; Virulence (Microbiology); Virulence - drug effects; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature25178

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. Two hypervirulent ribotypes of the enteric pathogen Clostridium difficile , RT027 and RT078, have independently acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose, suggesting a correlation between the emergence of these ribotypes and the widespread adoption of trehalose in the human diet. The rise of an intestinal epidemic Clostridium difficile is an intestinal pathogen and a major cause of antibiotic-associated diarrhoea. In epidemics in recent years, hypervirulent ribotypes that cause severe disease have emerged, but the factors that contribute to their emergence are unclear. In this study, Robert Britton and colleagues show that two phylogenetically distinct hypervirulent ribotypes, RT027 and RT078, have independently acquired mechanisms to metabolize low concentrations of the disaccharide trehalose. The team also show that this ability to metabolize trehalose correlates with disease severity in a humanized mouse model. These data suggest a correlation between the emergence of these ribotypes and the widespread adoption and use of trehalose as a sugar additive in the human diet.