Congenic strains of serotype A Cryptococcus neoformans

A血清型新型隐球菌的同源菌株

• 批准号: 6603508
• 负责人: BRIAN WICKES
• 金额: $ 14.6万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6603508
• 关键词: Cryptococcus neoformans; fungal genetics; genetic mapping; genetic markers; genetic strain; laboratory mouse; microorganism classification; microorganism reproduction; serotyping; virulence

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.

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，其中艾滋病患者的风险最大。隐球菌病通常表现为脑膜炎，这对于艾滋病患者来说通常被视为无法治愈，可能需要终生抗真菌治疗。感染遍及世界各地，大约 90-95% 的感染是由 A 血清型菌株引起的。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集和资助。然而，我们选择的菌株是 D 血清型菌株，它引起的感染占所有感染的比例不到 10%。选择该菌株是因为存在性相容菌株（指定为 MATα 和 MATa），而由于不存在可育的 MATa 菌株，因此无法获得相容血清型 A 菌株。新型隐球菌交配的另一个重要意义是，几乎所有感染都是由一种交配类型（MATalpha）引起的。 我们最近鉴定了一种 A 血清型 MATa 菌株，该菌株具有繁殖力，并且能够与 A 血清型 MATα 菌株（包括 H99 菌株）（该血清型的标准实验室菌株）有效杂交。该菌株的存在为研究新型隐球菌提供了强大的工具，因为它将使传统的遗传学研究能够在血清型 A 菌株中进行。该提案包含三个目标。第一个目标是制备两个仅交配类型不同的同源菌株对。遗传标记将被插入这些菌株中，使它们成为未来遗传和分子研究的有用工具。第二个目标将测试交配类型在毒力中的作用。通过在这些实验中使用同源菌株，可以独立于非交配型信息来测试交配型基因座处的信息在毒力中的作用。在最后一个目标中，将克隆并绘制血清型 A MATa 交配型基因座以确定其大小。目前，C. neoformans var. 的四个交配型位点中的三个。新型隐球菌（由血清型 A 和 D 组成）正处于不同的表征阶段。血清型 A MATa 基因座的分离将完成这项研究，由于交配类型在毒力中发挥的作用，这项研究意义重大。