# Role of host fucose in cholera toxin action

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $354,733

## Abstract

Cholera toxin is an AB5 toxin secreted by the human pathogen Vibrio cholerae. Cholera toxin binds to, enters,
and intoxicates human intestinal epithelial cells, causing the diarrheal disease cholera. Using a metabolically-
incorporated photocrosslinking sialic acid analog developed in the prior granting period, we showed that
cholera toxin interacts directly with fucosylated glycoproteins displayed on the surface of human colonic
epithelial cell lines. Further, host cell surface display of fucose is critical to the ability of cholera toxin to enter
and intoxicate host cells. During the upcoming granting period, we will define the fucosylated glycan
structures recognized by the B subunit of cholera toxin (CTB). The results of these experiments will provide
insight into the molecular basis for human variation in susceptibility to cholera. In addition, information
gained in these experiments will be used to design synthetic molecules that can interfere with cholera toxin
action and could potentially be used either clinically, either as prophylactics or therapeutics. We will also
investigate the relative roles of the two glycan binding pockets on CTB – the canonical GM1 binding site and
the novel fucosylated glycan binding site. We will determine which glycans are bound in each site, how the two
binding sites contribute to CT mechanism of action, and whether there is any interplay between the glycan
binding sites. Finally, we will explore how receptor identity affects the efficiency of CTB internalization, the
endocytic pathway for CTB internalization, and the ability of CT to intoxicate host cells. The results of these
experiments will reveal fundamental mechanisms of CT action and may provide new insight into the molecular
basis of endocytic mechanism.

## Key facts

- **NIH application ID:** 9983746
- **Project number:** 5R01GM090271-11
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jennifer J Kohler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,733
- **Award type:** 5
- **Project period:** 2009-09-30 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983746

## Citation

> US National Institutes of Health, RePORTER application 9983746, Role of host fucose in cholera toxin action (5R01GM090271-11). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9983746. Licensed CC0.

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