Congenic strains of serotype A Cryptococcus neoformans

描述（由申请人提供）：新型隐球菌是一种重要的人类真菌病原体，可引起危及生命的感染。感染本质上是机会性的，通常发生在免疫功能低下的患者中，艾滋病患者的风险最大。隐球菌病通常表现为脑膜炎，艾滋病患者通常无法治愈，需要终生抗真菌治疗。全世界都有感染，大约90- 95%的感染是由血清A型毒株引起的。这种真菌作为病原体的重要性导致了基因组测序项目的征求和资助。然而，所选择的菌株是血清型D菌株，它导致的感染不到所有感染的10%。选择该菌株是因为存在性相容菌株（指定为MATalpha和MATa），而由于缺乏可育的MATa菌株，无法获得相容的血清型A菌株。新生C.虫交配的另一个重要意义是，几乎所有的感染都是由一种交配类型（MATalpha）引起的。

DESCRIPTION (provided by applicant): Cryptococcus neoformans is an important human fungal pathogen that can cause life-threatening infections. Infections are opportunistic in nature and typically occur in immunocompromised patients, with AIDS patients being at greatest risk. Cryptococcosis is usually manifested as meningitis, which is often treated as incurable in AIDS patients and can require life-long antifungal therapy. Infections are worldwide with approximately 90- 95% of all infections being caused by serotype A strains. The importance of this fungus as a pathogen resulted in the solicitation and funding of a genome-sequencing project. The strain that was chosen, however, was a serotype D strain, which causes less than 10% of all infections. This strain was chosen because sexually compatible strains (designated MATalpha and MATa) exist, whereas compatible serotype A strains are not available due to the absence of a fertile MATa strain. An added significance of mating in C. neoformans is that virtually all infections are caused by one mating type (MATalpha). We have recently identified a serotype A MATa strain that is fertile and crosses efficiently with serotype A MATalpha strains, including strain H99, the standard laboratory strain for this serotype. The existence of this strain provides a powerful tool for studying C. neoformans because it will enable traditional genetic studies to be performed in serotype A strains. This proposal consists of three aims. The first aim will prepare two congenic pairs of strains that differ only in mating type. Genetic markers will be inserted into these strains to make them useful tools for future genetic and molecular studies. The second aim will test the role of mating type in virulence. By using congenic strains in these experiments, the role of information at the mating type locus in virulence can be tested independent of non mating-type information. In the last aim, the serotype A MATa mating type locus will be cloned and mapped to determine its size. Presently three out of the four mating type loci of C. neoformans var. neoformans (comprised of serotype A and D) are in various stages of characterization. Isolation of the serotype A MATa locus will complete this study, which is significant because of the role that mating type plays in virulence.