# Discovery of pertussis toxin receptors

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $246,000

## Abstract

Bordetella pertussis is the causative agent of pertussis, also known as whooping cough. Among
the virulence factors produced by B. pertussis, the ABs toxin called pertussis toxin (PT) is
strongly linked to disease symptoms and severity. Like other AB5 toxins, the PT holotoxin has
five B subunits that recognize cell surface molecules and one A subunit that harbors an ADP-ribosylation
activity. The nonulosonic acid N-acetylneuraminic acid (NeusAc) is commonly
described to be the receptor for PT but it is unknown how other glycan features affect PT
binding. Additionally, PT has been reported to bind to non-sialylated glycoconjugates. This
proposal aims to define the glycoconjugate features that mediate PT recognition and
intoxication of lymphocyte and respiratory epithelial cell surfaces, two cell types that are
proposed to be targets of PT action in vivo. In Aim 1, CRISPR/Casg genome-wide knockout (KO)
screening will be used to identify genes that impact PT binding to cell surfaces. Based on the
results of these screens, individual KO cell lines will be constructed and assayed for PT binding,
PT internalization, and PT intoxication. KO cell lines will also be evaluated for changes in
glycosylation, to reveal which glycan structures are associated with susceptibility to PT. In Aim
2, photocrosslinking sugar technology will be used to identify protein component of
glycoproteins that interact directly with PT. Based on the results of this analysis, KO cell lines
will be constructed and assayed for PT binding, PT internalization, and PT intoxication.
Together, the two aims will reveal the glycan and protein components of PT receptors. This
information will explain how PT targets specific cell types and may suggest strategies to
interfere with PT action therapeutically.
Project Summary/Abstract

## Key facts

- **NIH application ID:** 10903681
- **Project number:** 1R21AI183574-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Jennifer J Kohler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,000
- **Award type:** 1
- **Project period:** 2024-05-22 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903681

## Citation

> US National Institutes of Health, RePORTER application 10903681, Discovery of pertussis toxin receptors (1R21AI183574-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10903681. Licensed CC0.

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