Genetic Control of C. albicans Biofilm Formation

白色念珠菌生物膜形成的遗传控制

• 批准号: 7339677
• 负责人: AARON P MITCHELL
• 金额: $ 36.37万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7339677
• 关键词: Architecture; Bacterial Adhesins; Biological Assay; Candida albicans; Catheters; Cell Wall; Cells; Defect; Depth; Development; Devices; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Transcription; Genomics; Goals; Human; Implant; In Vitro; Infection; Medical Device; Membrane Proteins; Microarray Analysis; Microbial Biofilms; Modeling; Molecular Profiling; Monitor; Phenotype; Protein Overexpression; Proteins; Rattus; Regulation; Regulatory Pathway; Research Personnel; Resistance; Risk Factors; Role; Screening procedure; Structure; Surface; Surveys; Testing; Tissues; Transcription factor genes; Treatment Efficacy; Venous; Zinc Fingers; antimicrobial drug; base; factor C; genome sequencing; in vivo; in vivo Model; microbial; mutant; novel; pathogen; trait; transcription factor

Candida albicans is a major human fungal pathogen, causing both mucosal and deep tissue infections. A significant risk factor for C. albicans infection is the presence of an implanted medical device, which provides a surface for biofilm formation. The biofilm creates a protected microenvironment for survival of the pathogen. The immediate goal of studies here proposed is to define the key C. albicans genes and regulatory pathways that govern biofilm formation, with the long-term objective of developing new treatment strategies based upon this understanding. We have implemented a new strategy for analysis of unique C. albicans traits: a transcription factor function survey. With this strategy, we create strains with defects in each transcription factor gene and test the strains for phenotypic defects. We then use microarray analysis to identify target genes that have a direct role in phenotype under study. We have thus far tested homozygous insertion mutants in each of 84 transcription factor genes for biofilm defects. Zinc-finger protein Bcr1 p is required for biofilm formation and for expression of a group of surface protein genes and adhesins. We will analyze single and multiple target gene mutants as well as overexpressing strains in assays for biofilm formation. In addition, we will identify target genes for additional biofilm regulators that we define in our screen. Target genes will be subjected to functional analysis. Finally, we will test our in vitro results with a rat central venous catheter model for biofilm formation in vivo. Attributes including viable burden, biofilm architecture, and gene expression profiles will be monitored.

白色念珠菌是一种主要的人类真菌病原体，可引起粘膜和深部组织感染。一个