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Updated: Sep 15, 2025

Bioluminescent Bacterial Imaging In Vivo
Published on: November 4, 2012
Bacteria deliver a microtubule-binding protein into mammalian cells to promote colonization
Abstract:
Pathogenic Bordetella bacteria infect the ciliated respiratory epithelia of mammalian and avian hosts. Several bacterial proteins mediate host cell adhesion, but filamentous hemagglutinin (FhaB) is a principal adhesin because mutants lacking this protein exhibit profound colonization defects. Here, we show that FhaB carries a C-terminal microtubule-binding domain (FhaB-CT), which is translocated into the host-cell cytoplasm to promote bacterial colonization. Cryogenic electron microscopy of microtubule-bound FhaB-CT shows that the domain binds primarily to α-tubulin through a network of polar interactions. Live-cell microscopy of infected tracheal explants reveals that FhaB-CT delivery is required for Bordetella to occupy a niche at the base of cilia on airway epithelia. Finally, we demonstrate that the microtubule-binding domain is required for long-term colonization of the mouse nasal cavity by B. pertussis . These observations suggest that the FhaB-CT domain is delivered into motile cilia, where it interacts with axonemal microtubules. We propose that Bordetella initially adhere to the tips of cilia, then deploy multiple FhaB adhesin molecules to migrate to the base of the cilial forest. This mechanism enables Bordetella to resist removal by the mucociliary 'escalator' that clears the respiratory tract of microbes and debris.
Insights
Pathogenic Bordetella bacteria use filamentous hemagglutinin (FhaB) to bind host cell microtubules. This FhaB domain helps bacteria colonize the respiratory tract by anchoring them to cilia.
Area of Science:
- Microbiology
- Cell Biology
- Structural Biology
Background:
- Pathogenic Bordetella bacteria are significant respiratory pathogens.
- Filamentous hemagglutinin (FhaB) is a key adhesin mediating Bordetella colonization.
- Bordetella colonization defects are observed in mutants lacking FhaB.
Purpose of the Study:
- To investigate the role of the C-terminal domain of FhaB (FhaB-CT) in Bordetella colonization.
- To elucidate the mechanism by which FhaB-CT mediates bacterial adhesion and persistence.
Main Methods:
- Cryogenic electron microscopy (cryo-EM) to determine the structure of FhaB-CT bound to microtubules.
- Live-cell microscopy of infected tracheal explants to visualize FhaB-CT delivery and localization.
- In vivo colonization assays in a mouse model of Bordetella pertussis infection.
Main Results:
- FhaB-CT binds to α-tubulin in microtubules via polar interactions.
- FhaB-CT translocation into host cells is essential for Bordetella to establish a niche at the base of cilia.
- The microtubule-binding domain of FhaB is critical for long-term colonization of the mouse nasal cavity by B. pertussis.
Conclusions:
- Bordetella bacteria deliver FhaB-CT into host cilia to interact with axonemal microtubules.
- This interaction allows Bordetella to migrate to the base of cilia, evading mucociliary clearance.
- FhaB-mediated microtubule binding represents a novel mechanism for bacterial respiratory tract colonization.
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