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Bordetella adenylate cyclase is a virulence associated factor and an immunoprotective antigen
N Guiso1, M Rocancourt, M Szatanik
1Unité d'Ecologie Bactérienne, Institut Pasteur, Paris, France.
Abstract:
Bordetella pertussis and Bordetella parapertussis are both causative agents of whooping cough outbreaks. Although not expressing the pertussis toxin, B. parapertussis induces, in a murine model, an acute hemorrhagic edematous alveolitis, similar to that observed with B. pertussis. These data suggest that the pertussis toxin may only play an accessory role in the acute pulmonary syndrome observed during Bordetella infection. Both with B. pertussis and B. parapertussis, the ability to induce lethal pulmonary lesions is associated with enhanced in vitro adenylate cyclase expression and activity. We also demonstrate that passive immunization with specific anti-B. pertussis adenylate cyclase antibodies or active immunization with purified B. pertussis secreted adenylate cyclase protect mice against a lethal respiratory challenge with B. pertussis or B. parapertussis. Our results suggest that adenylate cyclase might be the primary cytotoxin responsible for mouse pulmonary lesions during respiratory tract infection with B. pertussis or with the related species B. parapertussis and is a protective antigen of B. pertussis.
Insights
Bordetella parapertussis causes severe lung inflammation similar to Bordetella pertussis, suggesting adenylate cyclase is the main toxin. Immunization against this toxin protects mice from both infections.
Area of Science:
- Microbiology
- Immunology
- Pathology
Background:
- Bordetella pertussis and Bordetella parapertussis cause whooping cough.
- B. parapertussis induces lung injury despite lacking pertussis toxin, suggesting other virulence factors are involved.
Purpose of the Study:
- To investigate the role of adenylate cyclase in Bordetella-induced pulmonary lesions.
- To evaluate adenylate cyclase as a potential vaccine target against Bordetella infections.
Main Methods:
- Murine models of B. pertussis and B. parapertussis respiratory infection.
- Assessment of lung pathology, including acute hemorrhagic edematous alveolitis.
- Measurement of adenylate cyclase expression and activity.
- Evaluation of protection conferred by active and passive immunization with adenylate cyclase.
Main Results:
- B. parapertussis infection caused lung lesions similar to B. pertussis.
- Enhanced adenylate cyclase expression and activity correlated with lethal pulmonary lesions in both infections.
- Immunization with anti-adenylate cyclase antibodies or purified adenylate cyclase protected mice against lethal Bordetella challenge.
Conclusions:
- Adenylate cyclase is likely the primary cytotoxin responsible for lung lesions in B. pertussis and B. parapertussis infections.
- Adenylate cyclase is a promising protective antigen for vaccines against whooping cough.