C ALBICANS IN THE GI TRACT ENVIRONMENT

胃肠道环境中的白色念珠菌

基本信息

批准号：
9765139
负责人：
CAROL A. KUMAMOTO
金额：
$ 50.51万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-23 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9765139
关键词：
Adherence Adverse effects Affect Antibiotics Back Benign Blood Candida albicans Catechols Cells Clostridium difficile Communities Development Dioxygenases Disease Disease susceptibility Enteral Environment Enzymes Epithelial Cells Epithelium Event Gastrointestinal tract structure Gene Expression Genes Goals Health Health Promotion Host resistance Human Immune response Immunocompromised Host Individual Infection Intervention Knowledge Learning Light Measures Metabolic Microbe Modeling Molecular Mus Organism Oxidative Stress Patients Play Population Predisposition Prevention Proteins Reactive Oxygen Species Recombinant DNA Recovery Research Research Project Grants Resistance Role Stream Superoxide Dismutase Testing Time antimicrobial base biological adaptation to stress commensal bacteria fungus gut colonization gut microbiota host colonization host microbiota improved member metabolome metabolomics microbial microbial community microbiota microorganism mutant novel pathogen pathogenic bacteria reconstitution response transcription factor

项目摘要

This research project investigates the interactions between colonizing Candida albicans cells and the GI tract environment. GI colonization with C. albicans is common for humans and generally does not have adverse effects on human health. However, if a patient becomes immunocompromised, colonizing C. albicans cells can escape the GI tract, reach the blood stream and cause disseminated disease. GI colonization is therefore significant because disease-causing fungal cells arise from the populations that colonize the host as harmless commensals. In addition, preliminary results show that, under certain conditions, colonization with C. albicans increases the resistance of the host to lethal challenge with an enteric bacterial pathogen. The long term goals of the proposed research are to understand the mechanisms by which C. albicans alters the GI tract environment and affects host resistance to challenge. The focus of Specific Aim 1 is to identify C. albicans activities that detoxify antimicrobial compounds. In Specific Aim 2, the goal is to understand how C. albicans alters the metabolite milieu of the GI tract. The studies proposed in Specific Aim 3 will analyze the effects of C. albicans colonization on the composition of the gut microbiota. These studies will increase the understanding of the interplay between C. albicans and the mammalian GI tract environment. Deeper understanding will enable development of novel interventions that harness the beneficial effects of C. albicans in the GI tract.

该研究项目研究定植白色念珠菌细胞与胃肠道环境之间的相互作用。白色念珠菌在胃肠道定植对于人类来说很常见，并且通常不会对人类健康产生不利影响。然而，如果患者免疫功能低下，定植的白色念珠菌细胞可能会逃离胃肠道，到达血流并导致播散性疾病。因此，胃肠道定植具有重要意义，因为引起疾病的真菌细胞来自作为无害共生体定植于宿主的群体。此外，初步结果表明，在某些条件下，白色念珠菌的定殖增强了宿主对肠道细菌病原体致命攻击的抵抗力。拟议研究的长期目标是了解白色念珠菌改变胃肠道环境并影响宿主对挑战的抵抗力的机制。具体目标 1 的重点是确定白色念珠菌解毒抗菌化合物的活性。具体目标 2 的目标是了解白色念珠菌如何改变胃肠道的代谢环境。具体目标 3 中提出的研究将分析白色念珠菌的影响定植对肠道微生物群组成的影响。这些研究将增进对白色念珠菌与哺乳动物胃肠道环境之间相互作用的了解。更深入的了解将有助于开发新的干预措施，以利用白色念珠菌在胃肠道中的有益作用。