# Diet driven evolution of epidemic ribotypes of Clostridium difficile

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $396,250

## Abstract

The emergence of pathogens that cause increased morbidity and mortality is a major public health
concern. Clostridium difficile is a major cause of hospital acquired infection and is the leading cause of
antibiotic-associated diarrhea. In the past decade, two epidemic ribotypes (RT027 and RT078) of C. difficile
have emerged as major ribotypes in hospital outbreaks around the world despite not being observed at
significant levels prior to the year 2000. These ribotypes are associated with increased morbidity and mortality
and have been classified as hypervirulent. However, the mechanistic basis for why these strains began to
emerge in the early 2000s is unclear.
 We have found that RT027 and RT078 strains have acquired the ability to grow on the disaccharide
trehalose more efficiently than other ribotypes of C. difficile. Our preliminary data shows that the mechanistic
bases for the improved growth in these two ribotypes are genetically and mechanistically distinct, suggesting
convergent evolution of improved trehalose metabolism in these phylogenetically distinct ribotypes. In addition,
we have found that disrupting the ability of a RT027 strain to utilize trehalose dramatically attenuates disease
severity, suggesting that trehalose metabolism contributes to the hypervirulent nature of RT027 and RT078
strains. Trehalose, a disaccharide of glucose, became a widely used food supplement after being granted
GRAS status approval by the FDA in 2000 and EFSA in Europe in 2001. Trehalose has a number of desirable
properties as a sugar additive due to the alpha, alpha 1-1 linkage that is heat and acid stable, which renders it
45% less sweet than sucrose. Normally found in foods such as mushrooms and shellfish, trehalose is now
added to numerous food and drink products ranging from ground beef to ice cream.
 The addition of trehalose to the worldwide food supply coincides with the first reports of RT027 and
RT078 strains in the early 2000s, even though these ribotypes were present in hospitals as far back as 1985.
We propose that addition of increased levels of trehalose to the food supply has selected for RT027 and
RT078 strains due to their ability to more efficiently metabolize trehalose and has contributed to hospital
epidemics. We will use two recently developed models in our laboratory, human fecal minibioreactor array
model of C. difficile invasion and a humanized microbiota mouse model of C. difficile infection, to study the
impact of trehalose and improved trehalose metabolism on the ability of RT027 and RT078 strains to cause C.
difficile infection. We will also investigate the mechanistic bases for improved trehalose metabolism of RT027
and RT078 strains. Finally, we will assess what impact improved trehalose metabolism has on colonization
dynamics, disease severity and carriage in animals of these hypervirulent C. difficile ribotypes. The following
specific aims are proposed: Aim 1. Investigate the mechanism of how trehalose metabolism by C.
di...

## Key facts

- **NIH application ID:** 10291417
- **Project number:** 5R01AI123278-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** ROBERT A BRITTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2017-11-17 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291417

## Citation

> US National Institutes of Health, RePORTER application 10291417, Diet driven evolution of epidemic ribotypes of Clostridium difficile (5R01AI123278-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10291417. Licensed CC0.

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