Antifungal drug target prioritization using Cryptococcus neoformans

使用新型隐球菌进行抗真菌药物靶点优先排序

基本信息

批准号：
8418700
负责人：
ALEXANDER IDNURM
金额：
$ 18.75万
依托单位：
UNIVERSITY OF MISSOURI KANSAS CITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-15 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8418700
关键词：
Acquired Immunodeficiency Syndrome Adrenal Cortex Hormones Agrobacterium Animal Model Animals Antifungal Agents Arthrodermataceae Ascomycota Aspergillus fumigatus Basidiomycota Bioinformatics Biology Candida albicans Clinic Clinical Communicable Diseases Communities Complex Cosmetics Coupled Cryptococcus neoformans Data Deposition Development Diploidy Disease Drug Design Drug Targeting Drug resistance Essential Genes Fission Yeast Fungal Genes Fungal Genome Future Gene Targeting Genes Genetic Genetic Screening Goals Growth Health Heterozygote Homologous Gene Human Immunocompromised Host Infection Institutes Life Medical Modeling Molecular Mutate Mycoses Nature Organ Transplantation Organism Outcomes Research Pharmaceutical Preparations Phylogenetic Analysis Recurrence Relative (related person)Research Resistance Resources Saccharomyces cerevisiae Serotyping Skin Surface Symptoms System T-DNA Techniques The science of Mycology Transplant Recipients Yeasts base chemotherapy clinically relevant drug development functional genomics fungal genetics fungus gene function innovation insight member mutant novel therapeutics pathogen positional cloning small molecule

项目摘要

DESCRIPTION (provided by applicant): Fungal diseases in humans are extremely common. They include mild cosmetic symptoms, recurrent skin and mucosal surface infections, and the rarer life-threatening diseases caused by disseminated fungi particularly in immunocompromised patients such as those suffering from AIDS, undergoing chemotherapy or corticosteroid therapy, and organ transplant recipients. Currently there is a limited repertoire of drugs available to treat fungi. Some species are naturally resistance to these drugs and resistance can be acquired in clinical settings. Thus, there is an urgent need to develop new treatments for fungal diseases. The objective of this proposal is to identify suitable targets for drug development in fungi, using a model organism Cryptococcus neoformans (in phylum Basidiomycota). This fungus is very diverged and different from commonly studied pathogenic or model species like Candida albicans, Saccharomyces cerevisiae or Schizosaccharomyces pombe (in phylum Ascomycota), and thus discoveries made in this organism are expected to extend across all pathogenic fungi. The specific aim of the proposed research is to identify essential genes of C. neoformans, using two experimental approaches. Essential genes are those required for viability: because mutants cannot grow, the identification of essential genes is a technical challenge. Here these genes will be identified by an innovative genetic screen and through a bioinformatic prioritization to essential genes found in fungi but not in humans. The proposal will also generate a resource of heterozygous strains suitable for small molecule studies utilizing haplo-insufficiency. The discovery of these essential genes represents new avenues for the development of antifungal agents.

描述（申请人提供）：人类的真菌疾病非常普遍。它们包括轻度的美容症状，复发性皮肤和粘膜表面感染，以及由传播真菌引起的稀有生命疾病，尤其是在免疫功能低下的患者中，例如患有艾滋病患者，接受化学疗法或皮质类固醇治疗的患者，以及有机体移植物。目前，有限的药物可用于治疗真菌。一些物种自然抗这些药物，并且可以在临床环境中获得抵抗力。因此，迫切需要开发真菌疾病的新疗法。该提案的目的是使用模型有机体Neoformans（在Phylum basidiomycota中）确定真菌中药物发育的合适靶标。这种真菌的分歧很大，与经常研究的致病性或模型物种不同，例如白色念珠菌，酿酒酵母或精神分裂症pombe（在天基菌中），因此在这种生物体中发现的发现有望延伸到所有致病性燃料中。拟议的研究的具体目的是使用两种实验方法鉴定新构型梭菌的必要基因。基本基因是生存力所需的基因：由于突变体无法生长，因此对基因基因的识别是技术挑战。在这里，这些基因将通过创新的遗传筛选以及通过在真菌中发现的基本基因而不是在人类中发现的基本基因的生物信息学优先级来鉴定。该提案还将产生适用于利用单倍不可易于的小分子研究的杂合菌株资源。这些基本基因的发现代表了开发抗真菌剂的新途径。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

'Division of labour' in response to host oxidative burst drives a fatal Cryptococcus gattii outbreak.

DOI：
10.1038/ncomms6194
发表时间：
2014-10-17
期刊：
NATURE COMMUNICATIONS
影响因子：
16.6
作者：
Voelz, Kerstin;Johnston, Simon A.;Smith, Leanne M.;Hall, Rebecca A.;Idnurm, Alexander;May, Robin C.
通讯作者：
May, Robin C.

Exploring and exploiting the connection between mitochondria and the virulence of human pathogenic fungi.