Effect of Pertussis Toxin on Cough in Guinea Pig

描述（由申请方提供）：百日咳杆菌是一种革兰氏阴性细菌病原体，可引起百日咳或百日咳。在呼吸道细菌感染后，该疾病的特征是严重和长时间的咳嗽，在症状最严重时频繁发作性咳嗽，然后在几周或几个月内以降低的频率复发。虽然B.百日咳在自然界中是人类特有的病原体，小型实验动物模型，如小鼠和大鼠，已被用于研究B方面。百日咳呼吸道感染和疾病，各种毒力因子的作用，以及对这种感染引起的免疫反应。然而，尚未开发出与人类百日咳疾病相关的咳嗽症状的代表性和方便的模型。豚鼠是咳嗽机制研究的一个有吸引力的模型，因为它们的咳嗽病理生理学的许多方面，包括引起咳嗽和气道高反应性的刺激，以及气道反应的药理学，与人类咳嗽非常相似。然而，豚鼠以前未用于研究B。呼吸道的百日咳感染。在本提案中概述的研究中，我们的目的是测试使用豚鼠作为小动物模型的可行性，以研究与B呼吸道感染相关的咳嗽疾病。百日咳。特别是，我们将解决的假设，百日咳毒素，一个主要的毒力因子产生的B。百日咳，在引起或改变咳嗽病理学中起主要作用。我们的具体目标是：1.阐明B的特性。豚鼠呼吸道的百日咳定殖，包括B的野生型和百日咳毒素缺陷型菌株。百日咳;和2.以确定B.豚鼠呼吸道的百日咳感染或者诱发咳嗽反应本身，或者改变由常用的咳嗽刺激诱导的咳嗽病理生理学，以及百日咳毒素在这些作用中所起的作用。

DESCRIPTION (provided by applicant): 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.