# Receptor-triggered toxin delivery mediated by FhaB of Bordetella

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2021 · $184,282

## Abstract

Project Summary
Filamentous hemagglutinin (FHA) is an important virulence factor of Bordetella pertussis, the causative agent of
whooping cough, and is thought to function as an adhesin that facilitates bacterial attachment to host cells. FHA
is a processed form of its precursor, FhaB, and it lacks a large C-terminal region found in FhaB. Our recent
results lead us to hypothesize that this C-terminal region functions as a toxin/effector delivery device to
modulate mammalian host cell function. The goal of this proposal is to test this hypothesis by examining the
topology of FhaB before and after binding to target mammalian cells. Towards this goal, we will leverage new
technologies recently developed by us. These methods include a heterologous and functional E. coli FhaB
expression system that will allow us to assess FhaB-dependent binding and cellular intoxication and a
fluorescent dye-based method that allows tracking of engineered FhaB proteins before and after bacterial binding
to target mammalian cells. We will also tag putative toxin domains to determine if they enter target cells, and we
will track them using microscopy and biochemical methods to follow their localization and fate. Because
additional factors in Bordetella spp. could contribute to mammalian cell intoxication, we will complement our
analyses with orthogonal approaches using wild-type and engineered Bordetella. In a second aim, we will assess
the effects of FhaB fragments on host cell physiology, extending our preliminary studies that indicate that C-
terminal fragments of FhaB induce human lung cells to change shape and lose viability. We will express
fragments of FhaB in multiple pathogen-relevant cell types and study their effects on cellular physiology and cell
viability. The information generated in this proposal has direct potential application to improving the FHA
component of the vaccine by including portions of the FhaB C-terminal toxin delivery system. Moreover, FhaB
would be the first example of a single bacterial protein that can deliver toxins into eukaryotic cells, which might
be potentially harnessed for therapeutic applications.

## Key facts

- **NIH application ID:** 10128803
- **Project number:** 1R21AI151728-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Diego Acosta-Alvear
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $184,282
- **Award type:** 1
- **Project period:** 2020-11-27 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128803

## Citation

> US National Institutes of Health, RePORTER application 10128803, Receptor-triggered toxin delivery mediated by FhaB of Bordetella (1R21AI151728-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10128803. Licensed CC0.

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