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.

项目摘要/摘要 粘附性是决定生物能否在非生物表面生存和传播的关键因素。 这种附着也是生物膜形成的第一步，生物膜与持久性和 抗真菌药物耐药性。金黄色念珠菌是一种新出现的真菌病原体，可在医院引起疫情 设置。这很可能与它在表面上的粘附力和持久性有关，因为它的粘附力很低。 容量不太可能导致医院暴发。然而，潜在的细胞生物学和遗传电路 Auris附着在表面的能力尚不清楚。我们的长期目标是确定C.Auris是如何感觉到 并对非生物表面作出响应，以允许牢固的附着，从而持久，生物膜的形成，以及 变速箱。 这项申请详细介绍了实验，以解决我们对 参与金龟子粘附性的成分。我们认为，金龟子对环境线索有反应 通过增加对表面的粘附性，这种粘附性是一个关键的毒力特征。我们最近开发了 用于询问这种有机体的遗传工具，给了我们前所未有的力量来分析 C.Auris暴发。在目标1中，我们将使用正向和反向遗传方法来研究 粘附素和其他成分在金龟子附着在表面的能力。在目标2中，我们将测试 金黄色葡萄球菌通过转录调控黏附对特定环境胁迫作出反应的假说 效应器。我们将使用转录图谱实验和候选启动子分析来剖析 控制附件的调节电路。总而言之，这些研究将为金龟子是如何 可以调节依从性。