# The role of sugar transport in C. difficile colonization and disease

> **NIH NIH P20** · UNIVERSITY OF LOUISVILLE · 2024 · $273,874

## Abstract

Project Summary/Abstract
Clostridioides difficile infection (CDI) is still the most common cause of healthcare-associated infection despite
a concerted effort to reduce the incidence. Increasingly, C. difficile is found in the community among persons
with no recent healthcare contact. The long-term goal of this project is to identify novel therapeutic targets which
can be exploited to treat CDI and control the spread of C. difficile. The overall objectives in this application are
to (i) elucidate the specificity and redundancy of the sugar transporters under positive selection in C. difficile, (ii)
determine their role in disease, and iii) examine the impact of dietary sugar on asymptomatic carriage. The
central hypothesis is that C. difficile has evolved to better occupy niche space within the gastrointestinal tract
(GIT) by taking advantage of the modern sugar-rich diet. The rationale for this project is that determining the
specificity and importance of sugar transporters and downstream metabolism in C. difficile carriage and infection
sets up a robust scientific framework whereby new prophylaxis and treatment strategies can be developed. The
central hypothesis will be tested by pursuing three specific aims: 1) Elucidate the specificity, redundancy, and
influence on toxin production of evolving sugar transport genes, 2) Determine the effect of evolving sugar
transport genes on community invasion and disease, and 3) Investigate the role of sugars in niche establishment
and asymptomatic carriage. Under the first aim, clean deletions of sugar transporters previously shown to be
under positive selection in epidemic C. difficile will be generated and their effect on growth and toxin production
assessed. The second aim will determine the role of sugar transport in invasion using a novel in vitro bioreactor
assay and disease by utilizing a mouse model of CDI. Finally, aim three will assess the role of sugar availability
in asymptomatic C. difficile colonization by using toxin negative C. difficile strains and a novel 13 strain mouse
microbiota colonization model. The research proposed in this application is innovative, because it focuses on
the metabolic adaptation of C. difficile to carbohydrates and their role in asymptomatic carriage as well as
disease. This focus has the potential to lead to novel prophylactic strategies that can be used against C. difficile
before the emergence of the disease. The proposed research is significant as it will provide a solid scientific
justification for the continued examination of metabolism as a virulence mechanism in C. difficile and provide a
framework for the future study of novel prophylactic, intervention, and treatment options.

## Key facts

- **NIH application ID:** 10795833
- **Project number:** 5P20GM125504-07
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** James Tristan Collins
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $273,874
- **Award type:** 5
- **Project period:** 2018-03-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10795833

## Citation

> US National Institutes of Health, RePORTER application 10795833, The role of sugar transport in C. difficile colonization and disease (5P20GM125504-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10795833. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*