Biology subjects

Sebo, P.

Publications and source records attributed to Sebo, P..

3 recordsLinked to original sources

bioRxiv2026

C-terminal domain of the filamentous hemagglutinin FhaB is crucial for interaction of Bordetella pertussis with ciliated epithelial cells

Bordetella pertussis, the causative agent of whooping cough, produces a [~]370 kDa filamentous hemagglutinin FhaB that serves as a major bacterial adhesin in airway infection. FhaB is secreted via a two-partner secretion pathway and under in vitro culture conditions it is proteolytically processed to the shed [~]230 kDa FHA antigen used currently in acellular pertussis vaccines. We show that FhaB remains largely unprocessed during B. pertussis adhesion to ciliated airway epithelial cells and that its C-terminal domain (CT) is essential for the adhesin function of FhaB. CT deletion did not affect FhaB folding, secretion, or surface exposure, but abolished B. pertussis adhesion to primary human nasal ciliated epithelial cells, thus preventing bacterial colonization of the nasal mucosa and shedding and transmission of the pathogen in a murine nasal infection model. In situ cryo-electron tomography revealed a structural reorganization of the FhaB filaments upon contact with the cilia, presumably due to export of the CT from bacterial periplasm and its subsequent delivery across the ciliary membrane. These findings establish the CT of FhaB as a critical determinant of upper airway colonization by B. pertussis and identify the unprocessed FhaB as the biologically relevant adhesin form involved in airway infection. The revised model of FhaB biogenesis underpins its unique mode of action in pertussis pathogenesis and makes the CT domain to a candidate antigen for future pertussis vaccines.

microbiology↗

bioRxiv2025

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

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 -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.

microbiology↗

bioRxiv2020

Cytotoxicity of the effector protein BteA was attenuated in Bordetella pertussis by insertion of an alanine residue

Bordetella bronchiseptica and Bordetella pertussis are closely related respiratory pathogens that evolved from a common bacterial ancestor. While B. bronchiseptica has an environmental reservoir and mostly establishes chronic infections in a broad range of mammals, B. pertussis is a human-specific pathogen causing acute pulmonary pertussis in infants and whooping cough illness in older humans. Both species employ a type III secretion system (T3SS) to inject a cytotoxic BteA effector protein into host cells. However, compared to the high BteA-mediated cytotoxicity of B. bronchiseptica, the cytotoxicity induced by B. pertussis BteA (Bp BteA) appears to be quite low and this has been attributed to the reduced T3SS gene expression in B. pertussis. We show that presence of an alanine residue inserted at position 503 (A503) of Bp BteA accounts for its strongly attenuated cytotoxic potency. Deletion of A503 from Bp BteA greatly enhanced the cytotoxic activity of B. pertussis B1917 on mammalian HeLa cells and expression of Bp BteA{Delta}A503 was highly toxic to Saccharomyces cerevisiae cells. Vice versa, insertion of A503 into B. bronchiseptica BteA (Bb BteA) strongly decreased its cytotoxicity to yeast and HeLa cells. Moreover, production of Bp BteA{Delta}A503 increased virulence of B. pertussis B1917 in the mouse model of intranasal infection (reduced LD50) but yielded less inflammatory pathology in infected mouse lungs at sublethal infectious doses. This suggests that A503 insertion in the T3SS effector Bp BteA may represent an evolutionary adaptation that fine-tunes B. pertussis virulence and host immune response. Author summaryPertussis remains the least-controlled vaccine-preventable infectious disease and the mechanisms by which Bordetella pertussis subverts defense mechanisms of human airway mucosa remain poorly understood. We found that B. pertussis had the cytotoxic activity of its type III secretion system-delivered effector BteA strongly attenuated by insertion of an alanine residue at position 503 as compared to the BteA homologue of the animal pathogen B. bronchiseptica. This functional adaptation reduced the capacity of B. pertussis to suppress host inflammatory response and may contribute to an acute course of the pulmonary form of human infant pertussis.

microbiology↗