Phylogeny as a basis for molecular identification of pathogenic fungi

病原性真菌在免疫功能低下的宿主（例如艾滋病、移植患者）中引起潜在的危及生命的疾病方面变得越来越重要。许多新出现的真菌病原体对三唑类抗真菌药物具有固有的耐药性，尽管在实验室中具有明显的敏感性，但对已建立的药物的临床反应仍不理想。目前的真菌鉴定技术是不敏感的，非特异性的，缓慢的，劳动密集型的，需要熟练的人员来识别不太常见的真菌。为了通过及时选择最佳抗真菌方案来改善临床结果，并缩短从治疗开始到治愈的时间间隔，早期准确鉴定病原体至关重要，需要在培养后或直接从临床标本中快速鉴定到种属水平。正确的真菌鉴定只能实现，如果致病生物体和它们的分类之间的系统发育关系是解决。基因检测比形态学和生物化学差异的检测更可重复。该提案的重点是建立一个准确的致病真菌系统发育系统，这将构成普遍适用的分子鉴定系统的基础，并建立一个人类致病真菌分子参考数据库。该项目将为生命之树项目提供病原真菌的序列数据。该项目结合了经典真菌学，分子生物学，生物信息学和传染病方面的专业知识，以开发医学上重要真菌的准确遗传学，为建立可通过万维网访问的质量控制参考数据库提供了独特的机会。这将提供更快，更准确的致病真菌ID，这将导致更好的临床治疗。

Pathogenic fungi are becoming increasingly important in causing potentially life-threatening diseases in immunocompromised hosts (e.g. AIDS, transplant patients). Many of the emerging fungal pathogens are inherently resistent to triazole antifungal drugs and clinical responses to established drugs remain suboptimal, despite apparent sensitivity in the laboratory. Current techniques of fungal identification are insensitive, unspecific, slow, labour-intensive and require skilled personnel for the ID of less common fungi. To improve clinical outcomes by prompt selection-initiation of the best antifungal regimes, and to truncate the interval from initiation of therapy to cure, early, accurate identification of the causative agent is crucial, making a fast identification to the species level after culture or direct from clinical specimens a necessity. A correct fungal identification can only be achieved if the phylogenetic relationships between the pathogenic organisms and their taxonomy is resolved. Gene detection is more reproducible than detection of morphological and biochemical differences. The proposal focuses on the establishment of an accurate phylogenetic system of pathogenic fungi, which will form the basis of a universally applicable molecular identification system and to develop a molecular reference database for human pathogenic fungi. This project will contribute sequence data of pathogenic fungi to the Tree of Life project. This project unites expertise in classical mycology, molecular biology, bioinformatics and infectious diseases, to develop an accurate phylogeny of medically important fungi, providing a unique opportunity to establish a quality controlled reference database accessible via the world-wide-web. This will provide a faster and more accurate ID of pathogenic fungi, which will lead to better clinical treatment.