# Differential Effects of TcdB1 and TcdB2 in C. difficile disease

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2020 · $432,300

## Abstract

ABSTRACT
The most recent reports indicate Clostridioides difficile is the cause of over 400,000 cases of
gastrointestinal illness and nearly 30,000 deaths annually. A major factor in the virulence of C.
difficile is TcdB, an intracellular bacterial toxin that glucosylates small GTPases in targeted cells.
Our studies focus on determining the critical differences in TcdB1 and TcdB2, the two major
variants of TcdB. TcdB1 is produced by historical strains of C. difficile and TcdB2 is produced by
hypervirulent/epidemic strains of C. difficile. Understanding how these two forms of TcdB, which
share 92% identity, differ in critical steps in intoxication and immunogenicity provides insight into
underlying differences in virulence between historical and epidemic strains of C. difficile. Several
studies, including many from our group, have found that TcdB1 and TcdB2 differ in their
interactions with target cells, tropism, cytotoxicity, and immunogenicity. The objective of our work
is to identify and characterize the underlying molecular and cellular details of the factors
accounting for these differences in TcdB1 and TcdB2 activity. To continue this line of
investigation, three specific aims to i) Determine the underlying differences in the molecular
mechanism of TcdB1 and TcdB2 receptor binding and cell penetration, ii) Determine if TcdB2
subverts antigen presentation and limits humoral immunity to co-administered vaccine antigen
TcdB2Δ1769-1787, and iii) Construct and test strains of C. difficile expressing mutants of TcdB1
and TcdB2 will be pursued. These studies will provide further insight into the differences in TcdB1
and TcdB2, determine the contribution of TcdB to ineffective immune memory leading to relapse,
and test hypotheses related to specific TcdB functional activities in the context of C. difficile
infection. Overall, the findings from this work will enhance our understanding of C. difficile disease
at multiple levels and provide information needed to prevent and treat this serious human illness.

## Key facts

- **NIH application ID:** 9971289
- **Project number:** 2R01AI119048-06
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Jimmy D. Ballard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $432,300
- **Award type:** 2
- **Project period:** 2015-08-07 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971289

## Citation

> US National Institutes of Health, RePORTER application 9971289, Differential Effects of TcdB1 and TcdB2 in C. difficile disease (2R01AI119048-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971289. Licensed CC0.

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