BARTONELLA--A MODEL FOR AN AIDS OPPORTUNISTIC PATHOGEN

描述：（改编自申请人摘要）本研究的长期目标是深入了解巴尔通体在HIV合并感染患者机会性感染中的致病机制。hiv感染者的巴尔通体综合征包括严重甚至致命的感染，如细菌性血管瘤病、盆腔性肝炎、复发性菌血症、心内膜炎、猫抓病、神经视网膜炎和脑病。从临床观察来看，巴尔通体的发病机制有两种显著的表现：复发性和持续性血流感染和血管增生性病变，但这两种疾病的细菌发病机制尚不清楚，主要是因为没有动物模型存在。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发病机制，并利用该动物模型来表征宿主对感染的反应以及与B. henselae和B. quintana相关的毒力基因表达机制。申请人的第一个目标是通过使动物感染亨塞贝氏杆菌或昆塔纳贝氏杆菌，建立一个与艾滋病相关的机会性巴尔通体感染的动物模型，目的是诱导一种或两种终末疾病表现：持续血流感染和血管生成病变。二是利用该模型研究巴尔通体的发病机制（感染过程、病理改变、体液免疫反应）。通过动物模型的建立和对疾病病程、病理表现和哺乳动物宿主-细菌相互作用的后续研究，申请人希望能够深入了解包括宿主免疫反应和持续复发感染在内的巴尔通体发病机制的基础，最终改善hiv感染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.