Bacteria deliver a microtubule-binding protein into mammalian cells to promote colonization

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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