Bordetella pertussis is a gram-negative bacterial pathogen that causes the disease known as pertussis or whooping cough. After respiratory tract infection by the bacteria, the disease is characterized by a severe and prolonged cough, with frequent paroxysmal coughing episodes at the height of the symptoms that then reoccur with reduced frequency over several weeks or months. Although B. pertussis is a human-specific pathogen in nature, small laboratory animal models, such as mice and rats, have been used to study aspects of B. pertussis respiratory tract infection and disease, the role of various virulence factors, and the immune responses elicited to this infection. However, a representative and convenient model for the cough symptoms associated with pertussis disease in humans has not been developed. Guinea pigs represent an attractive model for mechanistic studies on cough, because many aspects of their cough pathophysiology, including the stimuli that elicit cough and airway hyperresponsiveness, and the pharmacology of the airway responses, are very similar to those of human cough. However, guinea pigs have not previously been used to study B. pertussis infection of the respiratory tract. In the study outlined in this proposal, we aim to test the feasibility of using guinea pigs as a small animal model for aspects of the cough disease associated with respiratory tract infection by B. pertussis. In particular, we will address the hypothesis that pertussis toxin, one of the major virulence factors produced by B. pertussis, plays a major role in eliciting or modifying the cough symptomology.
Our specific aims are: 1. To elucidate the characteristics of B. pertussis colonization of the guinea pig respiratory tract, including that of wild type and pertussis toxin-deficient strains of B. pertussis; and 2. To determine whether B. pertussis infection of the guinea pig respiratory tract either elicits a cough response itself, or modifies the cough pathophysiology induced by commonly used tussive stimuli, and the role that pertussis toxin plays in these effects.
| Carbonetti, Nicholas H (2007) Immunomodulation in the pathogenesis of Bordetella pertussis infection and disease. Curr Opin Pharmacol 7:272-8 |
