Genetic characterization of C. auris adhesion

耳念珠菌粘附的遗传特征

• 批准号: 10426555
• 负责人: Teresa R. OMeara
• 金额: $ 18.83万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-10 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426555
• 关键词: Address; Adherence; Adhesions; Adhesives; Antifungal Agents; Automobile Driving; Bacterial Adhesins; Biotin; Candida albicans; Candida auris; Cell Wall; Cellular biology; Centers for Disease Control and Prevention (U.S.); Clinical; Comparative Genomic Analysis; Complement; Cues; Data; Development; Disease Outbreaks; Exhibits; Foundations; Fungal Drug Resistance; Future; Gene Expression Profiling; Genes; Genetic; Genetic Screening; Genetic Transcription; Goals; Growth; Heterogeneity; Hospitals; Image; Immunocompromised Host; Individual; Infection; Knowledge; Life; Link; Maps; Mediating; Microbial Biofilms; Microscopy; Modeling; Molecular; Molecular Genetics; Morphology; Mutate; Mutation; Organism; Pathogenesis; Pathogenicity; Pathway interactions; Phenotype; Prevention; Process; Protein Family; Proteins; Regulation; Role; Signal Transduction; Single Nucleotide Polymorphism; Skilled Nursing Facilities; Skin colonization; Streptavidin; Stress; Surface; Testing; Therapeutic Intervention; Transcriptional Regulation; Variant; Virulence; Virulence Factors; Work; base; environmental stressor; experimental study; forward genetics; genetic approach; insight; microbial; mouse model; mutant; novel; pathogen; pathogenic fungus; promoter; response; reverse genetics; targeted treatment; tissue culture; tool; trait; transcription factor; transcriptome sequencing; transmission process

Project Summary/Abstract Adherence is a key factor determining whether organisms can persist and transmit on abiotic surfaces. This attachment also is the first step in the formation of biofilms, which are linked with both persistence and antifungal drug resistance. Candida auris, an emerging fungal pathogen, can cause outbreaks in hospital settings. This is likely linked with its ability to adhere and persist on surfaces, as strains with low adhesive capacity are less likely to cause hospital outbreaks. However, the cell biology and genetic circuitry underlying the ability of C. auris to attach to surfaces are not known. Our long-term goal is to identify how C. auris senses and responds to abiotic surfaces to allow for robust attachment, and thus persistence, biofilm formation, and transmission. This application details experiments to address a fundamentally important gap in our knowledge of the components involved in the adherence of C. auris. We propose that C. auris responds to environmental cues by increasing adherence to surfaces, and that this adherence is a key virulence trait. We recently developed genetic tools for interrogating this organism, giving us unprecedented power to analyze the genes required for C. auris outbreaks. In Aim 1, we will use both forward and reverse genetic approaches to investigate the role of adhesins and other components in the ability of C. auris to attach to surfaces. In Aim 2, we will test the hypothesis that C. auris responds to specific environmental stresses by transcriptionally regulating adhesion effectors. We will use transcriptional profiling experiments and candidate promoter analyses to dissect out regulatory circuitry controlling attachment. Together, these studies will advance new concepts for how C. auris can regulate adherence.

项目总结/摘要 粘附性是决定生物体能否在非生物表面持续生存和传播的关键因素。 这种附着也是形成生物膜的第一步，生物膜与持久性和 抗真菌药物耐药性。耳念珠菌是一种新出现的真菌病原体，可引起医院暴发流行 设置.这可能与其在表面上粘附和持久存在的能力有关，因为具有低粘合剂的应变 能力，不太可能导致医院爆发。然而，细胞生物学和遗传电路的基础， C.耳附着于表面是未知的。我们的长期目标是确定C。耳感 并响应于非生物表面以允许稳固的附着，并因此持久，生物膜形成， 传输 本申请详细描述了实验，以解决我们对生物医学的认识中的一个根本性的重要空白。 参与C.耳。我们建议C.耳对环境线索有反应 通过增加对表面的粘附，并且这种粘附是关键的毒力性状。我们最近开发 询问这种生物体的遗传工具，给了我们前所未有的力量来分析所需的基因， C.耳疾爆发。在目标1中，我们将使用正向和反向遗传方法来研究 粘附素等成分对C.耳附着于表面。在目标2中，我们将测试 假设C.耳通过转录调节粘附对特定环境应激的反应 效应器我们将使用转录谱实验和候选启动子分析来剖析 控制附着的调节电路。总之，这些研究将提出新的概念，如何C。Auris 可以调节依从性。