MOLECULAR TYPING OF PNEUMOCYSTIS CARINII

描述：（改编自申请人摘要）。的目标 建议的研究是确定卡氏肺孢子虫的多样性， 感染人类和各种动物的病毒 卡氏肺孢子虫基因组的变异，并研究其流行病学 卡氏肺孢子虫感染在研究者的 实验室已经发现，分离株在不同的核苷酸序列， 核rRNA基因的内部转录间隔区（ITS）， 这种变异可用于鉴定卡氏肺孢子虫的分离株， 感染人类基于迄今为止鉴定的ITS序列变异， 从人类分离的卡氏肺孢子虫理论上可分为6种 迄今为止，已经发现了其中的4种不同类型。初步 流行病学研究显示， 这些类型的分布。一些标本有不止一种类型的 ITS序列。将进行实验以确定2种类型是否 的ITS序列实际上代表了两种类型的生物。另一个目的 将是寻找额外的基因组位点， 用于卡氏肺孢子虫菌株分型的序列变异。这些 另外的分型方法可以使每个P的亚分类成为可能。 卡氏型。将开发方法来分型卡氏肺孢子虫， 人类以外的动物物种，因为初步结果表明， 一些卡氏肺孢子虫可以感染动物和人类。流行病学 将进行研究，以确定是否有特定类型的 卡氏肺孢子虫与某些基础疾病有关， 治疗，或临床表现，如传播。流行病学 研究将进一步确定每种类型的地理分布 并且可以允许检测卡氏肺孢子虫类型之间的毒力变异。 分型将允许比较初始和第二次分离株 以确定感染是复发还是再感染。 研究人员还表明，卡氏肺孢子虫生物体可以被 在环境空气中检测到，支持假设， 卡氏肺孢子虫感染可通过空气传播。的相对 卡氏肺孢子虫感染的重要性， 潜伏在肺部的微生物， 将确定生物体。在拟议的研究结束时， 研究流行病学所需的有效分子生物学工具 卡氏肺孢子虫将被确定，流行病学研究将 已经确定了卡氏肺孢子虫菌株的多样性， 具有特定临床特征的相关序列变异 卡氏肺孢子虫感染

DESCRIPTION: (Adapted from Applicant's Abstract). The goals of the proposed research are to determine the diversity of Pneumocystis carinii that infect humans and various animal species by defining sequence variations in the genomes of P. carinii and to study the epidemiology of P. carinii infection. Studies conducted in the investigator's laboratory have revealed that isolates vary in nucleotide sequence in the internal transcribed spacers (ITS) of the nuclear rRNA genes and that this variation can be used to identify isolates of P. carinii that infect humans. Based on the ITS sequence variations identified to date, P.carinii isolates from humans can theoretically be classified into 6 different types of which 4 have been found to date. Preliminary epidemiological studies have revealed differences in the geographic distributions of these types. Some specimens had more than one type of ITS sequence. Experiments will be performed to determine whether 2 types of ITS sequences actually represent 2 types of organisms. Another aim will be to search for additional genomic loci that have nucleotide sequence variations useful for typing P. carinii strains. These additional typing methods may enable subclassification of each P. carinii type. Methods will be developed to type P.carinii that infect animal species other than humans since preliminary results have suggested that some P.carinii may infect both animals and humans. Epidemiological studies will be conducted to determine whether specific types of P.carinii are associated with certain underlying diseases, response to therapy, or clinical manifestations such as dissemination. Epidemiologic studies will further determine geographical distribution of each type and may allow detection of virulence variation among types of P. carinii. Typing will allow comparison of isolates from initial and second infections to determine whether infections are relapses or reinfections. The investigator has also shown that P. carinii organisms can be detected in the environmental air, supporting the hypothesis that P.carinii infections may be transmitted by the airborne. The relative importance of P. carinii infections developed by the reactivation of latent organisms that reside in lungs and by acquiring exogenous organisms will be determined. At the conclusion of the proposed study, effective molecular biology tools needed to study the epidemiology of P.carinii will have been established, and epidemiological studies will have defined the diversity of P. carinii strains and will have correlated sequence variation with particular clinical characteristics of P.carinii infection.