# Investigation of the interaction of Bordetella FhaB adhesin with microtubules

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $215,485

## Abstract

Pertussis or whooping cough, despite widespread vaccination, remains a major human health
problem. Pertussis is highly infectious and is most dangerous for newborns, where 1/3 of
infected infants under one year old are hospitalized and one in a hundred of hospitalized babies
die. In the last decades, we have seen a resurgence in pertussis cases, which is believed to
stem from decreased efficacy of the vaccine. The current vaccine is composed of cellular
components of the causative agent of pertussis, Bordetella pertussis; a major component is the
protein Filamentous hemagglutinin protein (FHA). FHA is a virulence factor in Bordetella and is
essential for adherence and colonization in human hosts.
 FHA is the mature form of FhaB, following the loss of a signal peptide and FhaB’s C-
terminal region whereby it was proposed that this C-terminal region had no function. Notably,
FhaB has striking similarities to CdiA, the toxin carrying component of contact dependent growth
inhibition (CDI), whereby the C-terminal toxin domain of which is translocated into target
bacterial cells upon contact. Our recent work has shown that extreme C-terminal of FhaB
(FhaB-CT) is delivered into human cells, where it acts as a microtuble (MT) binding protein.
Thus, FhaB-CT likely has a role in Bordetella virulence. While FhaB is translocated into
eukaryotic cells and CdiA is translocated into bacterial cells; these similarities lead us to
hypothesize that FhaB is part of an uncharacterized anti-eukaryotic CDI system.
 This proposal aims to characterize the interaction of FhaB-CT with MTs and identify
other Gram-negative bacterial FhaB-CT domains with anti-eukaryotic activities. First, we will
determine the structure of the complex of FhaB-CT with MT using cryo-EM. Secondly, we will
identify other anti-eukaryotic FhaB-CT domains through in silico analysis. We will test these
domains for eukaryotic entry and toxin/adhesion activity.
 The results of this study will (1) lay the groundwork to further explore Bordetella virulence
and the activity of B. pertussis FhaB-CT, and (2) identify other FhaB-CT proteins that target
eukaryotic cells and characterize their activity. Not only could these results aid the development
of a new pertussis vaccine, but with an improved understanding of the interaction between FhaB-
CT and MTs we may also offer a new target for pertussis therapeutic development. Lastly, with
the discovery of FhaB-CT activity and a novel anti-eukaryotic CDI system, we have found a new
branch of CDI systems with direct correlation to human health that require investigation.

## Key facts

- **NIH application ID:** 10953204
- **Project number:** 1R21AI185695-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Shane Gonen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $215,485
- **Award type:** 1
- **Project period:** 2024-05-17 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10953204

## Citation

> US National Institutes of Health, RePORTER application 10953204, Investigation of the interaction of Bordetella FhaB adhesin with microtubules (1R21AI185695-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10953204. Licensed CC0.

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