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Role of adhesin release for mucosal colonization by a bacterial pathogen
Loic Coutte1, Sylvie Alonso, Nathalie Reveneau
1INSERM U447, Institut National de Sante et la Recherche Medical Institut de Biologie de Lille, Institut Pasteur de Lille, 1 rue Calmette, 59019 Lille Cedex, France.
Abstract:
Pathogen attachment is a crucial early step in mucosal infections. This step is mediated by important virulence factors called adhesins. To exert these functions, adhesins are typically surface-exposed, although, surprisingly, some are also released into the extracellular milieu, the relevance of which has previously not been studied. To address the role of adhesin release in pathogenesis, we used Bordetella pertussis as a model, since its major adhesin, filamentous hemagglutinin (FHA), partitions between the bacterial surface and the extracellular milieu. FHA release depends on its maturation by the specific B. pertussis protease SphB1. We constructed SphB1-deficient mutants and found that they were strongly affected in their ability to colonize the mouse respiratory tract, although they adhered even better to host cells in vitro than their wild-type parent strain. The defect in colonization could be overcome by prior nasal instillation of purified FHA or by coinfection with FHA-releasing B. pertussis strains, but not with SphB1-producing FHA-deficient strains, ruling out a nonspecific effect of SphB1. These results indicate that the release of FHA is important for colonization, as it may facilitate the dispersal of bacteria from microcolonies and the binding to new sites in the respiratory tract.
Insights
The release of filamentous hemagglutinin (FHA) by Bordetella pertussis is crucial for respiratory tract colonization. This bacterial adhesin facilitates pathogen dispersal and attachment to new sites during mucosal infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Pathogen attachment to mucosal surfaces is a critical initial step in infections.
- Adhesins are key virulence factors mediating this attachment.
- The role of extracellularly released adhesins in pathogenesis remains largely unstudied.
Purpose of the Study:
- To investigate the significance of adhesin release in bacterial pathogenesis.
- To elucidate the function of extracellular filamentous hemagglutinin (FHA) from Bordetella pertussis.
Main Methods:
- Utilized Bordetella pertussis as a model organism.
- Constructed SphB1-deficient mutants lacking the protease responsible for FHA release.
- Assessed bacterial colonization in a mouse respiratory tract model.
- Evaluated bacterial adherence to host cells in vitro.
Main Results:
- SphB1-deficient B. pertussis mutants showed significantly impaired respiratory tract colonization compared to wild-type.
- These mutants exhibited enhanced adherence to host cells in vitro.
- Colonization defects were rescued by administering purified FHA or coinfecting with FHA-releasing strains.
Conclusions:
- The release of FHA by B. pertussis is essential for effective colonization of the respiratory tract.
- Extracellular FHA likely promotes bacterial dispersal and attachment to new host sites.
- Adhesin release represents a novel virulence mechanism in mucosal infections.