BARTONELLA--A MODEL FOR AN AIDS OPPORTUNISTIC PATHOGEN

描述：(根据申请者摘要改编)拟议研究的长期目标是深入了解巴尔通氏杆菌在同时感染艾滋病毒的患者机会性感染期间的致病机制。艾滋病毒感染者的巴尔通氏综合征包括严重的、甚至是致命的感染，如杆状血管瘤病、疱疹病毒性肝炎、复发性菌血症、心内膜炎、猫抓病、神经视网炎和脑病。从临床上观察，巴尔通体的致病机制有两个显著的表现：复发和持续的血流感染和血管增生性病变，但对两者所涉及的细菌致病机制尚不清楚，这主要是因为没有动物模型。这些研究的直接目的是通过建立动物模型来研究巴尔通体的致病机制，并利用该动物模型来表征宿主对感染的反应以及与亨氏巴尔通体和昆塔纳巴尔通体相关的毒力基因表达机制。申请者的第一个目标是开发一种艾滋病相关机会性巴尔通体感染的动物模型，通过感染亨塞氏杆菌或昆塔纳杆菌感染动物，目的是诱导一种或两种终点疾病表现：持续性血流感染和血管新生病变。第二个目标是利用该模型研究巴尔通体的致病机理(感染过程、病理变化、体液免疫反应)。申请者希望通过发展动物模型和随后对病程、病理表现和哺乳动物宿主-细菌相互作用的研究，深入了解巴尔通体致病的基础，包括宿主免疫反应和持续和复发感染，最终将有助于改进艾滋病毒感染患者巴尔通体感染的诊断、治疗和预防。

DESCRIPTION: (Adapted from Applicant's Abstract) The long range objective of the proposed study is to gain insight into the pathogenetic mechanisms of Bartonella species during opportunistic infection of patients co-infected with HIV. Bartonella syndromes in HIV-infected patients include severe, even fatal infections such as bacillary angiomatosis, peliosis hepatitis, relapsing bacteremia, endocarditis, cat scratch disease, neuroretinitis and encephalopathy. From clinical observations, there are two striking manifestations of Bartonella pathogenesis: relapsing and persistent bloodstream infections and vascular proliferative lesions, yet nothing is known about the bacterial pathogenetic mechanisms involved in either, largely because no animal models exist. the immediate objective of these studies is to study the mechanisms of Bartonella pathogenesis by developing an animal model, and utilizing this animal model to characterize the host response to infection and mechanisms of virulence gene expression associated with B. henselae and B. quintana. The applicant's first goal is to develop an animal model for AIDS-associated opportunistic Bartonella infections in by infecting animals with B. henselae or B. quintana, with the goal of inducing one or both endpoint disease manifestations: persistent bloodstream infection and angiogenic lesions. The second goal is to utilize the model to study Bartonella pathogenesis (course of infection, pathological changes, humoral immune response). Through development of an animal model and subsequent study of the disease course, pathological manifestations and mammalian host-bacterium interactions, the applicants hope to gain insight into the basis for Bartonella pathogenesis including host immune response and persistent and relapsing infection, which will ultimately lead to improved diagnosis, treatment and prevention of Bartonella infection in HIV-infected patients.