Chromosome loss in the fungal pathogen C. albicans

真菌病原体白色念珠菌的染色体丢失

• 批准号: 6760497
• 负责人: ALEXANDER D JOHNSON
• 金额: $ 18.17万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-15 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6760497
• 关键词: Candida albicans; cell cycle; chromosome deletion; diploidy; flow cytometry; fluorescence microscopy; fluorescent in situ hybridization; fungal genetics; genetic mapping; genetic recombination; green fluorescent proteins; laboratory mouse; lethal genes; microarray technology; mitotic spindle apparatus; polymerase chain reaction; virulence

DESCRIPTION (provided by applicant): Candida albicans is the most common fungal pathogen, causing both mucosal and systemic infections, particularly in immunocompromised people. Until recently, this opportunistic pathogen was thought to be asexual, existing only as a diploid organism. However, a mating-type-like (MTL) locus was identified and genetic manipulation of it led to the laboratory construction of mating-competent strains of C. albicans. The products of mating are tetraploid strains that must undergo a reductional division to return to the diploid state if a complete sexual cycle is to be achieved. In C. albicans, this reductional division (from tetraploid to diploid) can occur by a non-meiotic mechanism involving concerted chromosome loss. The resultant diploids are themselves mating-competent, thereby completing a parasexual cycle in this organism. The goal of this study is to determine the mechanism of concerted chromosome loss in C. albicans, and to understand the role it plays in the life-cycle of the organism, with special emphasis on its possible role during infection. The pattern of chromosome loss from tetraploid strains will be mapped by taking intermediates in chromosome loss and hybridizing their DNA to Candida microarrays. This will reveal if certain chromosomes are lost preferentially, and whether they are lost in a prescribed order. Chromosome loss will also be examined by directly visualizing cells undergoing chromosome loss by microscopy. If chromosome non-disjunction is occurring then defects in the mitotic apparatus may be observed. The transcriptional profiles of diploid and tetraploid strains will also be compared. Particular emphasis will be placed on understanding the transcriptional program of tetraploid strains during chromosome loss. A major goal of these studies is to examine the role of the tetraploid and chromosome loss in infection. Therefore, the virulence of the tetraploid strain of C. albicans will be compared to that of diploid strains, and chromosome loss will be followed in models of infection. Finally, these studies will directly address whether Candida contains recessive lethal alleles in its diploid genome by construction of an allelic microarray. This will also allow recombination events that take place during the parasexual cycle of C. albicans to be identified.

描述（由申请人提供）：白色念珠菌是最常见的真菌病原体，引起粘膜和全身感染，特别是在免疫功能低下的人群中。直到最近，这种机会性病原体被认为是无性的，只以二倍体的形式存在。然而，鉴定了一个交配型样（MTL）位点，并对其进行遗传操作，从而在实验室构建了具有交配能力的白色念珠菌菌株。交配的产物是四倍体菌株，如果要实现完整的性循环，必须经过还原分裂才能返回到二倍体状态。在白色念珠菌中，这种减数分裂（从四倍体到二倍体）可以通过涉及协调染色体丢失的非减数分裂机制发生。由此产生的二倍体本身具有交配能力，从而在该生物体中完成了一个拟性循环。